Cox-2 Inhibitors and Rheumatoid Arthritis-Part III of a IV Part Article.
(2/19/14)- In our item dated 2/4/14 below, we stated that the Food and Drug Administration (FDA) had cleared Bayer AG’s non-steroidal painkilling medication Aleve to change its label to show it carried a lower risk of causing heart reactions than other drugs.
We apologize to our viewers but this was not an accurate statement The panel rejected the claim that this was so. The panel of experts convened by the FDA did not come to this conclusion. The panel voted 16 to 9 against it. Bayer sold $40 million of naproxen (Aleve) in 2012. The panel focused on prescription forms of the medication which usually were in larger dosages than the over-the-counter medication.
The committee also voted to allow a major study of Celebrex, ibuprofen and naproxen at the Cleveland Clinic and elsewhere to continue. This study is known as Precision.
(2/3/14)- If we go back into history, it would show, as does some of the earlier items in this article, that Merck & Co. voluntarily withdrew its pain killing drug Vioxx in 2004 because it increased the chances of adverse heart problems for users of the medication. Taking that into account it was interesting to note that the Food and Drug Administration (FDA) announced that a review of Bayer AG’s painkiller medication Aleve, or its generic version, naproxen, carries a lower risk of adverse heart reactions than rival drugs.
Other well-known naproxen drugs, or non-steroidal anti-inflammatory drugs (NSAIDs) include ibuprofen, sold under the brand names such as Motrin and Advil; and celcoxib, a prescription drug sold under the brand name of Celebrix by Pfizer Inc. Celebrex came under fire back in 2004 as a drug similar to Vioxx, but that not prove to be the case
(12/2/12)- The Food and Drug Administration has granted approval to Pfizer & Co.'s Xeljanz (tofactinib) pill for treatment of moderate to severe rheumatoid arthritis for those who did not benefit from or were unable to tolerate the standard oral treatment, methotrexate.
Xeljanz can be used by itself or in combination with methortrexate and certain other treatments. It is administered as a pill that is taken twice a day, while the gold standard for rheumatoid arthritis is Abbott Lab's Humira, which is administered by an injection twice a week.
The approval was granted for the 5 mg.dose of the drug, but further assessment is needed of the 10-mg dose before approval may be granted.
(12/31/10)- Regeneron Pharmaceuticals Inc. announced that the FDA had placed a "clinical hold" on its experimental pain drug REGNA475/SAR164877 that it had been co-developing with Sanofi-Aventis SA. The company said that there are no ongoing trials of the drug that are enrolling, or treating patients.
Regeneron's drug is similar in structure to Pfizer Inc.'s osteoarthritis drug tanezumab, which the company halted its trial after a small number of patients reported worsening symptoms that required joint replacement. It later suspended trials for tanezumab for chronic low-back pain and diabetes-related nerve pain.
(12/23/10)- The results of a study that recently appeared in The Archives of Internal Medicine concluded that older patients with arthritis who take narcotic-based drugs to relieve pain have a higher risk of bone fracture, heart attack and death when compared to those taking non-narcotic drugs such as Advil , Aleve and Motrin.
The review was financed by the federal Agency for Healthcare, Quality and Research, and was conducted by researchers at Brigham and Womens Hospital in Boston. According to Daniel H. Solomon, the study's lead researcher, "They (narcotic painkillers) seem to carry profound risks to cardiovascular system as well as increased risk fractures and appear to be associated with increased risk of death."
The study looked at a 6-year period of time for Medicare recipients in New Jersey and Pennsylvania who were found to have osteoarthritis or rheumatoid arthritis. The majority of patients were women in the 80-year or older category.
The patients were divided into 3 groups. One group received a narcotic-based painkiller. The second group took a nonsteroidal anti-inflammatory drugs such as Motrin, Advil or Aleve. The third group took a Cox-2 including Vioxx, which is no longer on the market.
The researchers concluded that the overall risk of death was twice as great for patients taking a narcotic painkiller when compared to those taking a non-steroidal anti-inflammatory drug. The cardiovascular risks posed by the narcotics were the same as for the Cox-2 drugs.
Patients in the narcotic group were four times more likely to experience a compound bone fracture, and were twice as likely to have a heart attack then were the users of the nonsteroidal drugs.
(11/9/10)- In 2004, Merck voluntarily agreed to withdraw its painkilling medication Vioxx from the marketplace. In 2007, the company agreed to pay $4.85 billion to settle thousands of lawsuits against the company in product-liability suits that arose as a result of usage of the drug.
Merck, in announcing its 3rd quarter results stated that it would set aside $950 million to pay to the government to resolve the criminal investigation of the company's research, marketing and selling activities involved with the drug. It is believed that this is the matter that the U.S. Attorney's Office in Boston had brought before a criminal grand jury investigation.
The company declined to comment on whether the settlement would involve a guilty plea, and also whether or not any of the company's executives would be criminally charged in the matter.
(7/7/10)- U.S. District Court Judge Eldon Fallon in New Orleans ruled in favor of Merck & Co., in a non-jury trial, in a case brought by the state of Louisiana, involving the pain killing medication Vioxx. Merck had withdrawn the medication from the market on September 30, 2004, because of the increased risk of heart attack, stroke and even death from usage of the drug.
Louisiana's attorneys had argued in the $20 million lawsuit that the state would have restricted usage of Vioxx for programs such as Medicaid had they known of the increased risks associated with the drug.
In the only other such case in which a court has ruled, a summary judgment was granted in favor of Merck in an action that had been brought by the Texas attorney general. There are still about a dozen similar lawsuits pending against Merck brought by state attorney generals.
(3/8/10)- An Australian Federal Court awarded 290,000 Australian dollars ($261,000) to Graeme R. Peterson, 59 in a Vioxx case against Merck Sharpe & Dohme (Australia).
The court found that Vioxx contributed to Mr. Peterson's heart attack in 2003, according to the judgment. Merck said in a statement that it would appeal the verdict. Slater & Gordon was the plaintiff's legal firm.
(2/17/10)- Merck & Co. and the Vioxx lawsuits continue to be in the news even though it has now been almost 5 years since the company withdrew the drug from the market. The company announced that it has agreed to pay up to $12.15 million in legal fees and improve its system of monitoring its drugs after they have come to market.
The settlement is pending final court approval and is intended to resolve state and federal shareholder "derivative" suits alleging that current and former Merck officers and directors breached their fiduciary duties in the handling of the Vioxx matter.
The company had previously announced that Michael Rosenblatt was appointed its chief medical officer. Please also note our item dated 8/13/09 below in reference to the company's settlement of some claims by some drug-benefit plans.
The U.S. Supreme Court still has pending before it a separate shareholder case, seeking billion of dollars in damages from the company. The U.S. Attorney's office in Boston still is conducting a criminal investigation of Merck in connection with its handling of the Vioxx matter.
The claims of some 310-plaintiff groups are still pending in various courts throughout the United States, as well as some cases still pending in Turkey and Australia.
Under the latest settlement, Merck has agreed to register and submit clinical-trial results to a registry required under federal law; appoint a chief medical officer; establish two committees to monitor drug safety; make certain governance changes on it board; amend its code of conduct; and maintain certain governance changes that the company had agreed to in prior legal settlements.
(8/13/09)- Merck & Co. disclosed that it expects to pay $80 million to settle litigation in which drug-benefit plans sought to recover their costs in paying for its now withdrawn from the market painkilling drug Vioxx.
About 190 claims by private, third-parry payers are pending in New Jersey and federal courts. In a regulatory filing, the company stated it has reached an agreement in principle with the plaintiffs to settle the claims for $80 million.
Merck booked a charge in this amount for the second quarter.
(5/7/09)- The FDA has finalized its rules as to the contents on warning labels on painkillers such as acetaminophen, Tylenol, and nonsteroidal anti-inflammatory drugs (NSAIDs) so that they properly warn about the risks of stomach bleeding and/ or liver damage.
NSAIDs include aspirin, ibuprofen, naproxen and ketoprofen and are sold under brand names that include Advil and Motrin.
The new warnings, will start to appear on both the drug package and the drug container over the next year. Warnings will be required for cough and cold medicines that contain these painkillers.
The agency first proposed these changes in 2006, but those warnings didn't address all the requirements as set in the final rule.
(2/1/09)- In December 2008, the FDA asked for new animal trials and other information before it would approved Roche Holding AG application for its rheumatoid-arthritis drug Actemra, which is also known as RoActemra. This action meant that it would be at least another 18 months before the drug could be launched in the U.S.
On the other hand, the European Union granted the drug approval to be sold in Europe. Roche announced that it would sell the biological drug in combination with an older pill to patients who failed to respond to existing therapies.
Japan's Chugai Pharmaceutical Co., which is majority owned by Roche, developed developed the drug, but Roche will own the right to sell the drug outside of Japan. Opponents for approval of the drug's sale point out the negative side effects including increased risk of osteoporosis and high blood pressure.
According to the Agency for Healthcare Research and Quality, in 2005, 21 million adults – approximately 9.5% of the adult population – either visited or called a doctor for a prescription to relieve them of pain caused by arthritis. The data also revealed that the incidence of arthritis varies widely between different ethnic groups, with 10.5% non-Hispanic white adults reporting having arthritis, compared with just 5.9% of Hispanic adults and 4.3% of non-Hispanic Asians. The condition also appears to afflict more women than men (11.9% versus 7.1%). Source: Arthritis: Use and Expenditures among U.S. Noninstitutionalized Population, 2005. Agency for Healthcare Research and Quality. November 5th 2008.
(9/7/08)- The Federal Drug Administration (FDA) has ordered stronger warnings to be added to the drug labels on four medications used to treat rheumatoid arthritis, saying they can raise the risk of possibly fatal fungal infections. The four drugs are Humira from Abbott Laboratories; Cimzia by UCB; Enbrel by Amgen Inc. and Remicade made by Centocor, a unit of Johnson & Johnson and Schering-Plough.
The agency is also investigating a possible link between these same four drugs and cancer in young patients. The FDA has received 30 reports of cancers, mainly lymphomas, in patients who began taking the drugs when they were 18 or less. This investigation is expected to take at least the balance of this year.
Dr. Jeffrey Siegel who heads the FDA's office that oversees arthritis drugs, said the agency became concerned after discovering that doctors seemed to be overlooking a kind of fungal infection call histoplasmosis. Of 240 cases reported to the agency, 45 resulted in deaths to the patients taking anyone of the drugs.
The infection, which mimics the flu, is prevalent in the mid-part of this country Patients should call their doctors if they develop persistent fever, cough, shortness of breath or fatigue, which can be signs of the infection.
(8/29/08)- U.S. District Court Judge Eldon Fallon in New Orleans, who is overseeing the Merck-Vioxx $4.8 billion lawsuit settlement in the federal court capped the fees for the plaintiffs attorney at the 32% level which is slightly less than normal. The company voluntarily withdrew the drug from the market in September 2004.
There are 871 law firms involved in the litigation.
"Limiting attorneys' fees to 32% of the new recovery means that the attorneys in this case will receive more than $1.55 billion," Judge Fallon wrote. Contingency fees usually run in the 33 1/3rd % to 40% ranges.
Judge Fallon gave several reasons for his ruling. Among them were the fact in reaching a global settlement in November meant less complex work for all the attorneys involved in the settlement. He also felt that he had a responsibility to keep fees reasonable, because most of the claimants are elderly and frail and were not in a favorable position to negotiate the most favorable contract terms with their lawyers.
(7/27/08)- Merck & Co. announced that it would start sending out checks for former users of the painkilling medication Vioxx beginning in August. The company has funded a $4.85 billion settlement amount that is expected to resolve almost 50,000 lawsuits arising from the Vioxx matter.
The company said that more than 97% of the eligible claimants enrolled in the settlement program had accepted the settlement pact, thus surpassing the threshold levels the company required for the deal to proceed. Merck thus waives its right to walk away from the settlement deal.
(6/3/08)- Two recent court decisions were victories for Merck & Co. in connection with lawsuits over its painkilling medication Vioxx, that the company withdrew from the market in September 2004. Thus the scorecard now reads 11 victories in 16 trials for Merck.
In one of the decisions, a state appeals court in Texas overturned a $26 million jury verdict against the company under state damage cap laws. The jury; had originally ruled that the plaintiff was entitled to an award of $253 million. For additional information on this case please see our item dated 9/22/06 below.
The appeals court found that there was "no competent evidence that a blood clot triggered by Vioxx ingestion" caused the death of Mr. Ernst in 2001.
In an entirely separate matter the Superior Court of New Jersey's Appellate Division tossed out punitive damages and some compensatory ones in two Vioxx cases tried simultaneously in 2006. A jury had awarded John and Irma McDarby $4.5 million of compensatory damages on product-liability claims, $9 million of punitive damages and $11,905 of additional compensatory damages based on the state's consumer fraud statute.
The court ruled that the jury should not have been allowed to award punitive damages against Merck or to find that the company had committed consumer fraud since the state law was preempted by the FDA approval of the drug. The court also ruled that there can't be verdicts on both consumer fraud and product liability in the same case. It allowed the $4.5 million compensatory award to stand.
To see more on this case please see our item dated 3/14/07 below. The New Jersey court also denied $135 of consumer-fraud damages awarded to plaintiff Thomas Cona. It also said that Merck is not responsible for more than $4 million of legal fees and costs awarded to the plaintiffs' lawyers in both cases.
The Supreme Court of the U.S. has on its docket for this fall a case involving a drug that was approved by the FDA. The key question involved in this case is if a federal agency approves something, does the state have the right to add its own qualifications to that approval?
Plaintiffs in the Merck settlement now face a June 30th deadline to the agreement, which would result in an average payment of roughly $100,000 a plaintiff before legal fees, or to opt out and continue with their individual lawsuit. As of the latest count about 95% of the eligible plaintiffs have agreed to the proposed settlement.
(5/5/08)- According to an article in the May 2nd edition of the Wall St. Journal Pfizer Inc. has reached settlements with three law firms representing more than 200 of the thousands who have sued the company over its pain killing medications Bextra and Celebrex. More than 3,000 patients have claimed that the drugs caused heart attacks and strokes.
The drugs are in the same class of drugs as is Merck's Vioxx for which settlement agreements have been reached as we discussed in several of our items below.
Unlike Vioxx and Bextra, Celebrex has continued to remain on the market, and as a matter of fact was Pfizer's 3rd best selling medication last year garnering over $2.3 billion in sales in 2007. Pfizer voluntarily withdrew Bextra from the market in April 2005 after it was tied to a potentially fatal skin condition.
Firms have been offered $40,000 to $50,000 a client to resolve the Bextra cases and as much as $200,000 a client to settle the Celebrex cases according to the Journal article. Pfizer has declined to comment on the article.
(3/14/08)- More than 44,000 people had signed on for the Merck-Vioxx settlement pact by the next cutoff date which was February 29th. Of the roughly 57,100 who registered for the settlement earlier this year, more than 44,000 have submitted all or some of the paperwork necessary for enrollment in the deal, according to a Merck spokesperson.
People who enrolled could be eligible to receive an interim payment later this year. Using these numbers, it means that about 77% of the total number of potential claimants have signed up for the settlement. Merck has said that it could withdraw from the agreement if less than 85% of the potential claimants fail to sign on, but the company has the option to agree to the settlement if even a smaller number of claimants sign up.
In addition to the 44,000, another 5,000 claimants whose eligibility is less certain have also submitted the paperwork for enrollment according to that same Merck spokesperson.
A lead plaintiffs' lawyer, Andy Birchfield said that the enrollment figures were "extremely encouraging."
(1/31/08)- Parties to the Merck Vioxx settlement announced that more than 57,100 claimants out of an estimated 60,100 registered their cases by the first deadline of January 15th. Lawyers for both sides, at a conference before Judge Eldon E. Fallon of the Eastern District Court in New Orleans added language to the settlement agreement saying that each plaintiff's attorney was "expected to exercise his or her independent judgment in the best interest of each client individually."
Judge Fallon stated that, "I'm satisfied that nothing in the agreement imposes on a lawyer any impermissible restriction on the practice of law." This additional language was enough to satisfy the attorneys who had brought a motion to strike the clause requiring them to recommend the settlement to their clients, or withdraw from representing any of their clients who did not go along with the agreement.
Kent Jarrell, Merck's Vioxx legal spokesman said, "There are no pending motions anywhere" related to the settlement plan.
Thus the next test of the settlement agreement comes on February 29th, when 85% of the 57,100 claimants must enroll their cases by submitting releases and medical records. According to the Merck spokesman, 3,035 claimants have already enrolled.
(1/16/08)- The two important deadline dates that were negotiated between Merck & Co. and the 6 legal firms for settlement of the Vioxx cases are here.
The first deadline in the process was January 15th, when all plaintiffs with a Vioxx-related case must register, whether or not their injuries would qualify for the settlement or not. Those that do not qualify to be part of the settlement group may still go to court in connection with their claim.
More than 28,000 of the estimated 60,800 claimant have submitted registration information so far, according to Andy Birchfield, a partner with Beasley, Allen, Crow, Methvin, Portis & Miles, P.C. in Montgomery, Ala., and one of the plaintiffs' attorneys who negotiated the settlement.
The next crucial deadline comes February 29th, when the estimated 45,000 plaintiffs with heart-attack and stroke cases that qualify for the settlement must enroll. This is the part of the agreement wherein 85% of the claimants must sign up for it to become effective, although Merck has the option of accepting the agreement even if less than 85% of the claimants agree to it.
If a claimant accepts the settlement, the attorney representing that plaintiff must sign a document saying that he/she does not represent any plaintiff who has not gone along with the settlement agreement.
On January 18th a motion will be heard before Judge Eldon E. Fallon of the Eastern District Court in New Orleans, who is overseeing the settlement in the federal courts, as to whether or not the provision requiring attorneys to recommend it to their clients and not represent any client who does not agree to it, is professionally ethical.
Plaintiffs lawyers estimate that, depending on various age and risk factors, settlement payments would range from $50,000 on the low end to $1.5 million on the high end, with an average above $200,000.
(12/23/07)- Included in the $4.85 billion Vioxx settlement agreement arrived at between Merck & Co. and the plaintiffs legal committee that we discuss in our item dated 11/11/07 is the proviso that if an attorney's clients agrees to be part of the settlement pact, that attorney can no longer continue to represent any plaintiff who does not go along with the agreement.
This provision was considered to be a critical part of the settlement agreement. In an emergency motion brought before Judge Eldon E. Fallon of the Eastern District Court in New Orleans, a group of 12 plaintiff's attorney firms are seeking to have that provision set aside. The petitioners allege that it created a conflict of interest for them, and opens them up to possible lawsuits by their clients down the road.. Grant Kaiser, a Houston lawyer who represents about 1,800 plaintiffs in Vioxx lawsuits is the lead petitioner for the motion..
Taken together this group represents about 6,000 of the roughly 50,000 plaintiffs suing Merck in the Vioxx matter. For the deal to take effect, 85% of all plaintiffs, as well as 65% of the plaintiffs, who have stronger cases because they took Vioxx continuously for more than 18 months, must agree to its terms.
(11/29/07)- U.S. District Court Judge Charles R. Breyer of San Francisco ruled that plaintiffs in the litigation involving Pfizer's statin drug Celebrex have not presented scientifically reliable evidence that the drug caused heart attacks or strokes when taken at a daily dosage of 200-milligrams.
The 200-miligram dosage is the most commonly prescribed dosage for the drug.
There are more than 3,000 Celebrex plaintiffs, according to the ruling, but it is not clear how many of them will be affected by the ruling.
Paul Sizemore, a plaintiffs' attorney with Girardi & Keese in Los Angeles, estimates that about 900 Celebrex cases involve patients who were prescribed the 200-milligram dosage.
(11/11/07)- Merck & Co. and the Vioxx plaintiffs committee announced that they had reached a settlement agreement in connection with the approximately 26,500 lawsuits still pending on this matter. The settlement calls for the company to pay a total of $4.85 billion into a fund that will be used to pay qualified plaintiffs for their claims.
Eighty five percent of the plaintiffs must agree to the settlement, and no matter how many people file claims, the company's pay-out is capped at $4.85 billion. Merck voluntarily agreed to withdraw Vioxx from the market in September 2004. Cases have been brought on both the federal and state level. Judge Eldon E. Fallon of the Eastern District Court in New Orleans, Louisiana has been overseeing the federal cases, while Judge Carol E. Higbee of the Superior Court of New Jersey is in charge of the state Vioxx cases in New Jersey.
In December 2006, the judges in Louisiana, New Jersey, California joined with Judge Fallon convened the plaintiffs' committee and the legal team representing Merck with the object of arriving at a settlement. The negotiations took place in Washington and New Orleans, with Douglas R. Marvin, a partner at William & Connelly, leading the negotiations for Merck, and Russ M. Herman, a New Orleans plaintiff's lawyer and past president of the Association of Trial Lawyers of America, representing the plaintiffs.
Forty-two states have statute of limitations that would preclude plaintiffs from bringing new suits against Merck in their jurisdiction. This means they must file papers indicating that they would be bringing a legal action on this matter within the specified period of time. The final agreement is 70 pages long, with several appendices.
Plaintiffs are not required to accept the settlement, but under the terms of the agreement their lawyers must encourage them to do so. The plaintiffs' attorneys would be precluded from being the attorney for them if they do proceed with their legal claims.
As we state in our item dated 10/14/07, the trial scorecard now reads 11 victories for Merck and 5 losses. Merck has stated that it expects to be able to make payments under the agreement as early as August 2008.
Merck will set up two funds, a $4 billion one for heart-attack claims and $850 million one for stroke claims. Claimants will have to pass three "gates" to be able to take part in the settlement. First a claimant will have to show medical proof of a myocardial infarction or ischemic stroke. Second, a claimant wil have to show documented proof that they received at least 30 Vioxx pills. Lastly, a claimant will have to show that a certain amount of Vioxx was received within 14 days before the claimed injury.
A point system will determine the ultimate amount of money that the claimant would receive for their share of the settlement pie.
Once 85% if the eligible claims have approved the settlement, a third-party administrator who will size up how strong a plaintiff's case may be. Once the administrator has made a decision, a plaintiff might still be able to appeal that decision by taking the matter before a "special master".
(10/14/07)- With its most recent victory in a trial before a six-member jury in the Circuit Court of Hillsborough County, Florida the trial scorecard now reads 11 victories for Merck and its painkiller drug Vioxx and 5 losses.
The product-liability suit had been brought by Refic Kozic, who blamed Vioxx for his 2001 heart attack at the age of 50. Mr. Kozac had suffered a heart attack nine weeks after he had started taking the medication. The three week trial resulted in a victory for Merck on all the counts that had been brought in the lawsuit.
(9/24/07)- New York state and New York City have joined half-dozen other states in bringing a law suit against Merck & Co. for its painkilling medication Vioxx, which the company withdrew from the market in September 2004. The suit alleges that the company wrongfully withheld information as to the negative side effects of the drug.
The suit was brought by the offices of Attorney General Andrew Cuomo and Mayor Michael Bloomberg, seeking restitution for the tens of millions of dollars allegedly spent on Vioxx through Medicaid and prescription drug assistance programs for the elderly between 1999 and 2004, and for punitive damages..
As noted in our item dated 9/8/07 the N.J.Supreme Court ruled recently that suits brought by third-party payers such as insurers and pension fund could not be brought as a consolidated nationwide class-action suit.
(9/8/07- A recent ruling by the N.J. Supreme Court reversed two lower court decisions, and thus forbids a class-action suit brought against Merck & Co. for its painkilling drug Vioxx. The state Supreme Court has the final say on this matter. This decision provides the company with a victory on this type of class-action suit on both the federal and state level. To see more on the federal ruling see our item dated 4/15/07.
The ruling does not affect the merits of the underlying suit, which sought reimbursement for as much as $9.6 billion in Vioxx purchases plus treble damages under the state's consumer fraud law. Christopher A. Seeger was the lead lawyer for the plaintiff, the International Union of Operating Engineers Local 68 in West Caldwell, N.J., and John Beisner, of O'Melveny & Myers led Merck's outside defense.
To date, Merck has spent $1.94 billion on Vioxx legal fees and has set aside $810 million in reserves to pay additional costs. There are over 28,000 lawsuits pending against Merck in connection with Vioxx, and the company has vowed to fight each on a case by case basis. Merck has not paid out a single penny yet in connection with any of the cases that it lost.
Merck has won nine and lost five of the Vioxx cases that have gone to trial. A new trial was ordered in one case, and two others ended in mistrials. The court based its decision on the fact that "common questions of fact or law do not predominate" in the claims. The plaintiff in this case was supported by more than a dozen entities that offer health-care benefits including prescription drug coverage.
(7/26/07)- At the same time as it announced its second quarter earnings report Merck & Co. also announced that it had added $210 million to its Vioxx legal defense fund. The company said that it now faces 26,000 lawsuits covering a total of 44,000 plaintiffs. Merck stopped selling Vioxx in September 2004.
(7/6/07)- Judge Eldon E. Fallon of the Eastern District Court in New Orleans, Louisiana rejected Merck & Co's attempt to throw out lawsuits brought by two people who began taking Vioxx after April 2002. It was some time after that date that the FDA had approved a new warning label for the drug that stated that it might increase the risk for heart attack or other cardiovascular problems.
Merck had asserted that this change in the label therefore warned any users of the drug that they had an increased risk for heart events, and thus precluded any suits from being brought against the company by post 2002 users of the drug.
A Merck spokesperson said that the company is considering an appeal of the ruling.
In a second blow to Merck, a new study, known as Victor, that was conducted by researchers at Oxford University in England, showed that there was an increased heart risk associated with Vioxx immediately after patients started taking the drug. A copy of this study was sent to New Jersey Superior Court Judge Carol E. Higbee who is overseeing all the Vioxx lawsuits being held in New Jersey.
The results of the Victor study will be published in the New England Journal of Medicine shortly. The new report included information about the risk of cardiovascular events, and did not discuss the colon cancer results.
There were 2,434 patients enrolled in the Victor study, which sought to determine if the drug could arrest the progression of colon cancer. The patients in the study were followed for a period of two years. The study was halted when Merck pulled the drug from the market because of the increased risk of heart attacks as shown in the Approve study.
The Victor study showed that 23 of the patients who had cardiocascular events, 16 of them were on the Vioxx and suffered a cardiovascular event within a one-year period of time. The study also suggested that by 14 days after the patients stopped taking the drug, the risk of heart attack or stroke went away.
(6/11/07)- Judge Eldon E. Fallon of the Eastern District Court in New Orleans, Louisiana, who oversees all Vioxx litigation in the federal court said that retired FBI Agent Gerald Barnett could accept a $1.6 million award or have a new trial on his claims that Vioxx caused his 2002 heart attack. The award includes $600,000 in compensatory and $1 million in punitive damages.
In the original trial the federal jury awarded the plaintiff Barnett $50 million in compensatory damages and $1 million in punitive damages. Judge Eldon threw out the award finding it "grossly excessive" and ordered a new trial on damages.
Barnett's lawyer than requested that the court determine a new award known as a remittur. Legal experts say remittiturs are not unusual in cases with large awards for pain and suffering. Legal experts noted that it was significant that Judge Fallon had upheld the amount of the punitive-damages since this would be useful in setting parameters for future settlement talks between Merck and the over 24,000 plaintiffs whose cases have yet to be tried.
Merck said that it would appeal the award.
In his award order, Judge Fallon noted that Mr. Barnett had undergone a preventive-treatment regimen and that this had enabled the plaintiff to be able to do many of the activities that he loved to do before his heart attack.
(4/28/07)- The Food and Drug Administration accepted the opinion of its advisory panel, and thus rejected approval for Merck's next generation pain killing drug Arcoxia. For more info on the panel's decision see our item dated 4/20/07 below. This decision had been expected since the FDA usually does follow the opinion of its advisory panels.
Arcoxia has been approved for sale in 63 countries and a Merck spokesman indicated that the company would continue trials of the drug to prove that it is just as safe as other drugs in the same category that have been approved by the agency.
(4/20/07)- An FDA advisory panel voted 20-1 against the Arcoxia, Merck latest generation Cox-2 painkiller drug intended to replace Vioxx, which was removed from the market in September 2004 for safety reasons. For more on this subject please see our item dated 4/9/07. Pfizer's Celebrex is the only Cox-2 painkiller still on the market in this country. It generated more than $2 billion in sales for the company in 2006.
Arcoxia is sold in 63 countries, though its use is limited. The FDA is expected to make its ruling on the drug by the end of this month, but it is rare for the agency to not follow the recommendations of the advisory panels. The panel feared that Arcoxia could cause as many as 30,000 heart attacks annually if it became a widely used drug.
Committee members said the drug held no treatment advantage over already existing drugs that outweighed concerns about the cardiovascular risks. The panel discussed the risk of some of the older pain relief medications that it had previously approved that have proven to increase the risk of heart attacks, but did not act on this subject.
The study done in connection with Arcoxia involved 34,000 arthritis patients. The original study compared the drug with naproxen (Aleve), and found that Arcoxia was about three times more dangerous to the heart and for strokes, so the company switched to comparing it with diclofenac. Merck claimed that Arcoxia was no more dangerous to the heart than was diclofenac.
Dr. John Jenkins, director of the Office of New Drugs at the FDA said, "We didn't know about these cardiovascular problems back in the '80s and'90s when the older drugs were approved." He then went on to say, "Some could question, should all those other drugs be out there."
(4/15/07)- Merck & Co. came in with victories in connection with the Vioxx lawsuits in both the federal and the state legal systems. It is expected that both these rulings will be appealed.
In the federal court matter, the judge ruled that the cases could not be consolidated into one action, but instead must be litigated on a case by case basis. Merck has been vehemently fighting the state cases on the one-on-one basis, since this substantially increases the costs to the plaintiffs in these actions. Even though it is more expensive for Merck to defend these lawsuits this way, it has a tendency to discourage plaintiffs from going to court with this matter.
Merck has won 10 of the cases that have gone to trial, while losing 5 of them so far. There are approximately 28,000 Vioxx related lawsuits pending in the various court systems. There are 3 states however where the court has consolidated the cases, and they are New Jersey, Texas and California. Over one-half of the pending state court actions are in New Jersey before Judge Carol E. Higbee of the Superior Court of New Jersey.
Judge Eldon E. Fallon in the Eastern District of Louisiana.is handling the federal trials.
In the Texas state court ruling, Harris County District Court Judge Randy Wilson, who is overseeing all of the Vioxx state court suits in that state, upheld the motion made by Merck to dismiss the lawsuit against them by Ruby Ledbetter, who blamed her heart attack on Vioxx. The judge said he is granting the motion to dismiss the case because of a recently issued ruling from the FDA.
That FDA ruling says that the agency's approval process supercedes state law in how manufacturers of health-care products must warn consumers about their risks. Please keep in mind that Merck withdrew Vioxx from the market in September 2004. The plaintiff's attorney said that he would appeal this ruling. If this ruling is upheld it would greatly impact the almost 1,000 other cases now pending against Merck for Vioxx in Texas. Please keep in mind that one state does not have to accept a ruling from another state, so we will have to wait and see how this ruling plays out.
(4/9/07)- Merck & Co.will appear before and FDA advisory panel seeking approval of its new painkiller drugs Arcoxia for the treatment of osteoarthritis. The drug is in the same class of drugs as is Vioxx, which is a Cox-2 inhibitor. The agency is expected to rule by the end of April on whether to approve Arcoxia.
Merck's study of Arcoxia was called Medal, and consisted of 34,701 patients enrolled in three trials. The study compared Arcoxia to the generic drug diclofenac.
To see more on this trial please see our article dated 12/23/06 below.
(4/3/07)- Jurors in an Illinois County court found for Merck and its painkiller drug Vioxx in a suit brought by the husband of a woman who died in 2003 after having been on the drug for 20 months. The case was decided in Madison County Illinois, a county that is known for siding with plaintiffs in these types of cases.
It was the first case tried in the Midwest, and with the verdict in favor of Merck, the scorecard now read 10 victories for Merck, 5 losses and two Los Angeles state-court cases resulting in mistrials on January 18. In addition, another 14 cases scheduled for trial were either dismissed or withdrawn from the trial calendar by plaintiffs before a jury could be selected.
As of December 31, 2006, the claims related to more than 4,025 alleged Vioxx users have been dismissed before being scheduled for trial. Of these cases, 1,225 were dismissed with prejudice.
Dan Ball and Stephen Strauss of Bryan Cave LLP in St. Louis and James Fitzpatrick of Hughes Hubbard & Reed LLP in New York represented Merck at this trial.
Frank Schwaller of Granite, Ill., sued Merck for wrongful death of his wife Patricia. Defense lawyers pointed out that Mrs. Schwaller was 5 feet 2 inches tall and weighed between 250 and 300 pounds, had several risk factors for heart disease, including obesity, diabetes, high blood pressure and a sedentary lifestyle.
Andy Crouppen, one of the lawyers for Mr. Schwaller, said the verdict would be appealed. Mrs. Schwaller was 52 years old at the time of her death.
After deliberatin for about 6 hours over 2 days, jurors ruled that the drug was not a "proximate cause" of the death of Mrs. Schwaller. The jury found that while Merck knew or should have known about the dangers of Vioxx, the company had adequately warned doctors and consumers about possible complication from using the drug.
(3/23/07)- Federal District Court Judge John Lifland in Newark, NJ upheld the validity of three Pfizer patents covering its painkiller drug Celebrex, after hearing arguments during a two-week trial in November.
The ruling, if upheld on appeal, means that Teva Pharmaceutical Industries of Israel can not come out with its generic version of the drug until July 2015. The drug generated $1.6 billion in sales for the company in 2006.
"The patents are neither invalid nor unenforceable and Teva has infringed the patents," Judge Lifland ruled in a 201-page opinion. Teva had sought FDA approval to sell 100-mg, and 400-mg doses of celecoxib, the main ingredient in Celebrex. Teva argued that the patents were invalid because previous inventions made the technology obvious.
Pfizer acquired Celebrex in its $60 billion purchase of Pharmacia Corporation in 2003
(3/14/07)- The New Jersey Superior Court jury awarded $47.5 million to Frederick "Mike" Humeston and his wife in the retrial of his case against Merck and its painkiller drug Vioxx. For more on the case see our item dated 3/4/07 below.
The jury found that Merck's handling of Vioxx was "oppressive, outrageous or malicious." It awarded Mr. Humeston and his wife $20 million in compensatory damages and $27.5 million in punitive damages. Merck said that it planned to appeal the verdict.
The Vioxx scoreboard now reads 9 victories for Merck and 5 loses, with two Los Angeles cases resulting in mistrials on January 18th
(3/9/07)- Judge Carol E. Higbee of the Superior Court of New Jersey rejected the motion of W. Mark Lanier, the attorney for Brian Hermanns, in the case we discussed in our item dated 3/4/07 below. The motion wanted the judge to throw out the jury verdict of non-negligence in favor of Merck and its painkiller drug Vioxx.
This ruling means that the most that Mr. Hermanns' estate can recover in the case against Merck is limited to the consumer fraud maximum of three times what he had paid for his Vioxx, plus about $2 million in costs and fees that his lawyer had requested.
The jury began the second phase of the Humeston case to determine if Vioxx caused his heart attack, and if so, the extent of the damages that he may be entitled to recover.
(3/4/07)- In the latest jury rulings from the state court in the Superior Court of New Jersey involving Vioxx, the plaintiff won one and Merck won the other. The split verdict involved two cases being tried jointly before Judge Carol E. Higbee in Atlantic City. In both cases, the eight-member jury ruled unanimously that Merck had committed consumer fraud by misleading doctors and patients, and by intentionally suppressing, concealing or omitting information about the risks of Vioxx.
The verdicts concluded the first phase of the trial, which dealt only with Merck's behavior. In the second phase, which will begin next week, the jury will decide whether Vioxx caused the September 2001 heart attack of the winning plaintiff Frederick Humeston, and what damages, if any should be awarded.
In the other case, the jury ruled that Merck had given adequate warning by the time the plaintiff, Brian Hermanns of Green Bay, Wis., died of a heart attack in September 2002 at the age of 44.
As a result of the Hermanns decision, the relatives of Mr. Herman could be entitled to payments only from the consumer fraud verdict, which is limited to three times the cost of the Vioxx, and lawyers' fees and expensed, but not compensatory and punitive damages resulting from his death.
Merck had revised the Vioxx label in April 2002 to add information about the heart risks, according to the lawyers.
Mr. Humeston had lost in his first trial against Merck in November 2005. Judge Higbee threw out that verdict after new evidence came to light that Merck had misrepresented the data on the risks of the drug in a scientific paper that was published in The New England Journal of Medicine in 2000. For more on the Humeston case please see our items dated 8/18/06, 11/8/05 and 11/4/05.
(1/30/07)- Merck & Co. announced that Angela McCool had dropped her lawsuit against the company for its painkilling drug Vioxx that was scheduled to go to trial in Philadelphia State Court in 5 weeks. In her suit Mrs. McCool alleged that the drug caused her husband's heart attack and death.
Five other lawsuits are set for trial between now and June, with the next one scheduled to begin in New Jersey state court before Judge Carol E. Higbee.
Excluding two mistrials in California, 18 cases have been scheduled for trial over Vioxx to date. Juries have ruled for Merck nine times, the plaintiffs have won four of the cases and five cases have been dismissed. Once these 5 other lawsuits have been adjudged, the pressure will be on both sides to negotiate a settlement for the whole class of cases.
The Appellate Division of the Superior Court of N.J. has reinstated the lawsuit that Judge Carol E. Higbee dismissed that sought to force Merck & Co. to pay for medical tests for people who took Vioxx for 6 continuous weeks between May 20, 1999 and September 30, 2004.
The appeals court sent the case back to Judge Higbee for further proceedings. Judge Higbee had ruled that medical-monitoring programs are intended for toxic-exposure cases and not for pharmaceutical products.
Judge Higbee will now have to decide whether to certify the proposed class action case that was instituted by plaintiffs Phyllis Sinclair and Joseph Murray
Novartis AG said that it would start selling its Cox-2 inhibitor Prexige across Europe starting in the next few months. The company also announced that it has completed the clinical trials necessary to resubmit the drug for FDA review this year. Merck & Co. has also announced that it will seek FDA approval to sell its Cox-2 pain-inhibiting drug Arcoxia. (see our item dated 12/23/06).
(1/20/07)- The latest state court decision in the Merck-Vioxx legal saga resulted in a hung jury in the California state court trial wherein Lawrence Appell, of Scottsdale, Ariz., and Rudolph Arrigale, of Westministry, California were the plaintiffs before Judge Victoria G. Chaney. The judge therefore declared a mistrial.
Thus the scorecard now reads as follows- Merck has now won 4 of the 5 cases that have gone to trial in the federal court. Of the 17 state court cases that have been scheduled for trial and are no longer pending, only four have resulted in a plaintiff's verdict. Jurors have decided in Merck's favor in 7 cases, and 5 cases have been dismissed, and now we have 1 case in which there is a hung jury.
The two California cases that were tried before a Superior Court jury that deadlocked when they reached the third question on a lengthy verdict form.
The jury did answer yes to the first question, finding that Vioxx did have potential risks or side effects that were known or knowable. The jury did also answer yes to the second question as to whether or not these risks presented a substantial danger to users of Vioxx.
The third question asked if the plaintiffs' doctors would have recognized the potential risks or side effects, and this is the question that caused the hung jury. It is not clear as to when there will be a retrial of these cases.
(12/28/06)- Judge Alex W. Gabert, the Rio Grande, Texas city court judge who heard the Leonal Garza case reduced the $32 million jury award to about $7.75 million so that it conformed to state law. The jury had ruled in favor of the plaintiff in April in one of the early Vioxx state trials, when it found that Merck's Vioxx was responsible for the 71-year old man's fatal heart attack in 2001.
The judge however refused to reverse the verdict in favor of the plaintiff. Travis Sales, a Merck defense attorney in the case said that the company will file a motion for a new trial within 30 days, based largely on a matter between one of the jurors and Mrs. Garza. In the post-trial discovery proceedings, the company found that the juror Jose Manuel Rios had borrowed thousands of dollars from Mrs. Garza over the years, but did not have any outstanding debt to her at the time of the trial.
After the verdict was issued, the company was ordered to pay the Garza family $7 million in non-economic compensatory damages and $25 million in punitive damages. The judge ordered the punitive damage reduced to conform to the 2003 Texas law that caps punitive damages at twice the amount of economic damages-lost pay-and up to $750,000 on top of non-economic damages.
Mr. Garza was retired at the time of his heart attack so the jury had not awarded any economic damages
(12/23/06)- Merck & Co. will seek FDA approval for lower level dosages of its painkiller Arcoxia, which is a Cox-2 inhibitor drug. The drug has been approved for sale in 62 other countries, and its application for approval in this country has been pending for several years already.
The company had hoped that the drug would be the next generation drug to replace Vioxx, which it had to remove from the market in 2004.
In addition to seeking approval for the two lower level dosages of the drug to treat symptoms of osteoarthritis the company hopes to gain approval for the higher dosage levels also. The FDA review of the application will last until April 2007. Merck had first applied for FDA approval for the drug in 2001, but it withdrew that application because it wanted to resubmit one that sought an additional use treating a spinal disorder known as ankyloingspondylitis. It resubmitted the application in 2003.
In October 2005 the FDA issued an "approvable letter" saying it needed additional safety and efficacy data before it could approve Arcoxia.
The additional safety data included a group study known as the Multinational Etoricoxib and Diclofenac Arthritis Long-Term program, or Medal. In August, Merck said that preliminary Medal data showed that the rate of confirmed thrombotic cardiovascular events such as heart attack was similar between Arcoxia and diclofenac (Voltaren made by Novartis AG of Switzerland).
The data also showed that people on Arcoxia discontinued the drug as a result of the side effect of high blood pressure at a greater rate than those on diclofenac.
(12/20/06)- A clear picture has developed at both the state court and federal court level that the weaker Merck-Vioxx trials are resulting in victories for the large pharmaceutical company in the weaker cases. Within a three-day period of time Merck has won Vioxx cases on both the federal and state court levels.
The Alabama state court case, that we noted in our item of 12/15/06 resulted in another victory for Merck. In the Alabama case, the jury of 8 women and 4 men returned the verdict in less than two hours in favor or Merck. In this suit, which was filed by Gary Albright, 57 of Chelsea, Ala., who claimed that Vioxx caused his heart attack, and that the company had failed to reveal potential dangers of the drug before pulling it from the market.
Mr. Albright had suffered his heart attack in 2001 after having used Vioxx as a painkiller for his arthritis for less than 18 months. Merck's lawyers argued that he was a high risk patient since he had diabetes, high blood pressure, high cholesterol and was overweight.
The scorecard now reads 4 to 1 in favor of Merck0-Vioxx on the federal level and 8 to 4 in favor of the same parties on the state level. California is the only state left where a state case is being heard this year that a decision is expected to be rendered this year.
(12/15/06)- Merck & Co., the Whitehouse Station, N.J. drug maker, has prevailed in the 5th Vioxx trial that went to a federal jury before Judge Eldon E. Fallon in the Eastern District of Louisiana. After deliberating for about an hour and a half, the jury of four women and three men found that Merck adequately warned the plaintiff's physician of Vioxx's risk, and that the drug did not cause the plaintiff's heart attack.
With this case now having gone to a jury, the scoreboard now reads four federal cases decided in Merck's favor, and only one federal case going against the company and its painkilling medication Vioxx.
In this particular case, Anthony Dedrick was a 51-year-old Wayne County, Tenn. resident who blamed the drug for his heart attack in 2003. He had taken Vioxx for a period of 6 months to treat his arthritis. His usage of the drug took place after Merck had updated the label to include precautions about the cardiovascular risk of the medication.
Merck had argued that Mr. Dedrick had a number of risks for heart attack, including diabetes, hypertension, high cholesterol, and a family history of cardiovascular problems. He had been a smoker for 35 years, and had a history of alcohol and cocaine abuse.
Judge Fallon has indicated that he would like the parties to the Vioxx litigation to meet to see if they can come to some settlement agreement in these federal cases. There are currently two other Vioxx case trials taking place in state courts in Alabama and California.
(12/5/06)- According to the results of a government sponsored study that was published recently online by Public Library of Science, a San Francisco nonprofit group, Bayer AG of Germany's pain relieving nonsteroidal anti-inflammatory (NSAID) drug Aleve did show an increased risk of heart attach and other cardiovascular events compared with a placebo. The study was ended prematurely so the results are not conclusive.
Aleve is a member of a class of drugs known as naproxen. The study followed 2,500 seniors across the U.S for a period of two years. Those on naproxen experienced cardiovascular death, heart attack, stroke, congestive heart failure and transient ischemic attack at a rate 63% higher than those in the placebo group.
Some members of the group were given Pfizer's Celebrex, another pain-relieving medication, and this group had a 10% higher level of cardiovascular events than did the placebo group. The government announced the halt of the study in December 2004, shortly after Merck pulled its pain-killing medication Vioxx from the market.
The NSAID group of drugs includes ibuprofen and diclofenac.
The NIH's National Institute on Aging started the Alzheimer's Disease Anti-Inflammatory Prevention Trial, or Adapt, in 2001 to test whether naproxen and Celebrex were effective in preventing Alzheimer's dementia or delaying cognitive decline in the elderly. Both Aleve and Celebrex were compared to a placebo. As concern grew because of the Vioxx problem, the study was terminated before any conclusive results could be obtained.
(11/27/06)- Judge Eldon E. Fallon of the Eastern District of Louisiana ruled that the federal lawsuits claiming death or injury from Merck & Co.'s Vioxx couldn't be pooled into one national class action lawsuit. This ruling pertains to federal lawsuits, but has no effect in regards to state court actions being pooled into a class action in a particular state.
Judge Fallon's 25-page ruling rejected the plaintiffs' argument that all cases should be tried in New Jersey, because the company should reasonably expect to follow the laws of the state where it is based. The judge went on to state that the company "should expect to abide by every jurisdiction's laws", not only the laws of New Jersey.
Judge Fallon went on to rule that the laws of New Jersey should not confine plaintiffs in states other than New Jersey. Russ M. Herman, chairman of a committee of plaintiffs' lawyers said he had expected the decision.
(11/21/06)- After deliberating for about 1-1/2 hours, a jury of two women and 5 men sitting in the federal court in New Orleans before U.S. District Judge Eldon Fallon of the Eastern District of Louisiana decided that Merck's Vioxx did not cause the heart attack in 2003 of Charles Laron Mason. The jury also rejected the Utah man's claim that the company had failed to adequately warn of the risk of Vioxx in causing heart attacks.
In the case, Mr. Mason claimed he took Vioxx for approximately 10 months before his heart attack. Even though Mr. Mason had been taking the drug for less than 18 months, the Plaintiff's Steering Committee had selected Mr. Mason's case as one that it wanted to go to trial.
Merck has now won 3 of the 4 cases that have gone to trial in the federal court. Of the 16 cases that have been scheduled for trial and are no longer pending, only four have resulted in a plaintiff's verdict. Jurors have decided in Merck's favor in 7 cases, and 5 cases have been dismissed.
New Jersey Judge Carol Higbee threw out the verdict in the Frederick "Mike" Humeston case in favor of Merck, and Judge Fallon overturned the damage award shortly after trial. The Humeston case is rescheduled for trial in New Jersey starting in January 2007.
The claims of more than 3,000 plaintiff groups, not yet scheduled for trial, have been dismissed. That includes more than1,100 plaintiff grups whose claims were dismissed with prejudice with by plaintiffs themselves or by the courts, meaning they can't be filed again. More than 2.000 additional plaintiff groups have had their claims dismissed without prejudice.
Phil Beck, Tarek Ismail and Shayna Cook of Bartlit, Beck Palenchar & SCOTT LLP of Chicago represented Merck in the Mason case, as it had done in all the previous federal cases.
It was shown during the Mason trial that Mr. Mason had multiple risk factors for a heart attack, including significant coronary artery disease, a family history of cardiac problems and he was considered medically obese.
Merck added an additional $598 million to its legal charges bringing litigation reserves for the Vioxx trials to a total $958 million excluding settlement costs. Judge Fallon has said that he wants to press for a settlement of all the federal Vioxx cases after the next one that goes to trial which is on November 27th in New Orleans.
(10/26/06)- Sharon Rigby has opted to drop her Vioxx related lawsuit against Merck & Co., in what was scheduled to have been the first coordinated proceedings before Texas state court judge Randy Wilson. The case had been scheduled to go to trial in Houston in November. As of last count there were over 23,800 lawsuits, nationwide pending against Merck.
Ms. Rigby had alleged that she had suffered a heart attack as a result of taking Vioxx over a period of time. Merck was prepared to defend itself in the action based on a defense that other risk factors had been the cause of her heart attack. These defense included the fact that Ms. Rigby had been a smoker and had a family history of heart attacks.
Vioxx was withdrawn from the market in September 2004, and the statute of limitation has run its course in most states and in the federal system of justice also. This means that there should not be too many more plaintiffs who will bring lawsuits against Merck in connection with the Vioxx matter, but it will be a long time before the court system will see the end of these lawsuits.
(9/28/06)- Let the scoreboard in the federal court Merck-Vioxx cases now read, 2 verdicts in favor of Merck-Vioxx, 1 verdict in favor of the plaintiff. Taking into account the 3 verdicts for each side in the state cases, the total scoreboard now reads 5 in favor of Merck and 4 in favor of the plaintiffs.
The latest case that was decided by the jury in favor of Merck took place in the Federal District Court in Louisiana, before Judge Eldon E. Fallon in New Orleans involved Robert Gary Smith (56) of Florence, Ky., who blamed his February 2003 heart attack on Vioxx. The Smith case is the first that involves a claim that occurred after Merck updated its label for Vioxx in 2002 to include some data on cardiovascular risk.
Mr. Smith claimed that he had taken Vioxx for a total of 138 days. The federal court jury of 6 women and 2 men deliberated for about 3 hours before deciding that Merck had adequately warned of the drug's heart risks and that the drug wasn't a proximate cause of Mr. Smith's heart attack. Mr. Smith had a number of heart attack risk factors, including obesity, high blood pressure and atherosclerosis.
The attorneys for Mr. Smith argued that Merck had played down the risk data by placing the cardiovascular-risk information in the label's precautions section, as opposed to the warnings section. Merck argued that the FDA had approved the updated label.
The next key legal decision in the Merck-Vioxx cases is expected from New Jersey State Court Judge Carol Higbee, in connection with a class action suit certification brought by union and third-party insurers against Merck. Philip Beck represented Merck in the Smith Louisiana lawsuit.
Additional cases to be tried this year include 2 Vioxx trials in federal court in New Orleans, 2 in state court in Alabama, and 1 in state courts in California and Texas.
(9/22/06)- Merck & Co. continues to show that it has adopted a hard-nosed defense in connection with the lawsuits against the company involving its painkiller drug Vioxx. As proof thereof, the company announced that it was putting up a bond in connection with its appeal of the verdict against the company by a jury in Texas that awarded the widow of Robert Ernst $253.4 million in total damages over a year ago.
The jury in semi-rural Angleton, Texas awarded the plaintiff $229 million in punitive damages on August 20, 2005, but Texas law caps punitive damages, so that amount will be reduced to a maximum of $26.1 million in the event the plaintiff prevails. Please see our item dated 8/20/05 for more on this case.
Robert Ernst was 59-years old at the time of his death in May 2001. He had taken Vioxx for 8 months before he passed away.
The appeal is based on two primary issues. Merck will argue that there was insufficient evidence that Mr. Ernst suffered any injury due to Vioxx, and also that it was improper to allow the testimony by a previously undisclosed witness mid-way through the trial. That witness was Dr. Maria Araneta, the Johnson County, Texas, assistant-coroner who did the autopsy on Esrnst. She was not on the plaintiff's pretrial witness list, but the judge allowed her testimony.
Dr. Aranetta testified that a heart attack probable killed Ernst, but that he died too quickly for his heart to show damage.
(8/31/06)- U.S. District Judge Eldon E. Fallon, who is presiding over the Merck & Co. Vioxx trials in the federal court in New Orleans, overturned the $50 million compensatory damage award that the plaintiff, Gerald Barnett won in the case that was decided on August 17th. For more details on this suit see our item dated 8/18/06.
Calling the $50 million jury award "grossly excessive", the judge ruled that a new trial must be held, and he also overturned the $1 million in punitive damages that the jury awarded Mr. Barnett. Judge Fallon noted that the 5th U.S. Circuit Court of Appeals ruled that if a new trial is ordered for compensatory damages, it must also include punitive damages.
The new trial will be limited to the question of damages, and will not be a retrial of the case. "No reasonable jury could have found" that Gerald Barnett was entitled to $50 million in compensatory damages from Merck because of the heart attack he suffered in 2002 was the reason why the judge set aside the amount of the verdict.
Barnett's past and future medical bills, his pain and suffering and other intangible losses are legitimate reasons for compensation. The judge went on to reason that, since Mr. Barnett is retired, lost wages and earning capacity have no bearing on the damages.
While his energy may have been reduced he apparently has returned to many of his daily activities. He may have lost 9 or 10 years of his life expectancy, which should be considered by the new jury.
(8/18/06)- Merck & Co. suffered a double loss yesterday in connection with the court trials of its pain killing medication Vioxx.
The first loss took place in the federal court in New Orleans where the jury, after deliberating for four hours, found that the company was negligent in failing to warn doctors about the risks of prescribing Vioxx. The jury awarded the plaintiff, Gerald Barnett, a 62- year old former FBI agent who had been taking the drug for over 4 years, $50 million in compensatory damages and $1 million in punitive damages. To see more about this case please see our item dated 8/9/06.
The jury found that Merck had "knowingly misrepresented or failed to disclose" information about Vioxx to Mr. Barnett and his doctors. The jury further found that the company had "acted in wanton, malicious, willful or reckless disregard for the plaintiff's rights."
This was the second Vioxx trial that was held in the federal court system, with the company having prevailed in the first suit in February.
The jury went on to find that the drug was the cause of Mr. Barnett's heart attack.
In the second setback of the day for Merck and Vioxx, New Jersey Judge Carol Higbee threw out the verdict in the Frederick "Mike" Humeston case that was decided by the jury in November 2005. For more information on this case please see our items dated 11/4/05 and 11/8/05.
Judge Higbee threw out the jury's decision because of the fact that additional evidence had come to the forefront after the decision regarding the crucial VIGOR study results that were published in the New England Journal of Medicine.
The Journal had issued an Expression Of Concern over the study, saying it did not include three additional heart attacks that occurred in patients taking Vioxx. A deposition given by the Journal's editor Gregory Curfman in connection with the study were the reasons given by Judge Higbee for tossing the decision .
A retrial will be held early next year. There are still 8 cases on the various courts calendars in connection with Vioxx that are scheduled to be heard this year.
(8/09/06)- After deliberating for more than 12 hours a jury of 12 ruled in Los Angeles Superior Court that Merck & Co. was not liable for causing 71 year old Stewart Grossberg's heart problems even though he had taken Vioxx for an extended period of time. Thus the Vioxx scoreboard now reads 5 victories for Merck and 3 defeats.
In the Grossberg case the jury ruled that Merck did not conceal information from Mr. Grossberg about the drug, and also that the drug did not cause his heart problem. Mr. Grossberg began taking the medication in 1999 to manage pain in his hand, and knees caused by osteoarthritis.
He suffered his first heart problem in 2001at which time a stent was placed in one of his arteries. Mr. Grossberg testified that he took the medication "as needed" and not daily. Mr. Grossberg than resumed taking Vioxx two years later but stopped taking it in August 2004 after hearing about problems with the drug. Three months later he experienced chest pains and had a second stent placement.
Judge Victoria G. Chaney has consolidated more than 2,000 Vioxx lawsuits in Los Angeles, California.
The next Vioxx lawsuit on the calendar is in federal court in New Orleans. It is the case of 62-year-old former FBI Agent Jerry Barnett before Judge Eldon Fallon. This will be the second case to be decided in the federal court system.
Barnett began to take pain relievers after an auto accident in 1978 and switched to Vioxx in January 2000. He had taken Vioxx for 31-months before his heart attack. His attorney, Mark Robinson, said Barnett exercised regularly, ate well and followed his doctor's advice to the letter.
(7/23/06)- Merck & Co. has prevailed in the latest case in connection with its painkiller medication Vioxx to go to a jury trial. Thus the scoreboard now stands 4 victories for the company, and 3 victories for the plaintiffs who sued in connection with their usage of the medication.
This case was decided in the New Jersey State court trial involving the 68-year-old plaintiff Elaine Doherty, who used Vioxx for over a 2-year period of time. For more on the prior New Jersey State court case please see our article dated 4/12/06 herein.
The 7-member jury, that deliberated for more than 9 hours over 2 days found that Merck had adequately warned Mrs. Doherty's doctor about the risks of taking Vioxx. The jury did also find, by a 7-0 vote, that the company failed to give adequate warning to Ms. Doherty, but it also found that Vioxx did not contribute substantially to her heart attack. No damages were awarded to Ms. Doherty
The jury also found that Merck was not guilty of consumer fraud in this case. Merck's defense showed that Ms. Doherty had a high cholesterol level was a diabetic with high blood pressure and was substantially overweight.
In voting 7-0 that the company's ads failed to adequately warn consumers of the risks of Vioxx the issue of direct-to-consumer ads by drug companies is once again thrust into the limelight. For more on this issue please see our article Research and Marketing of Drugs-a Challenge Part II
As of March 31 Merck still faces over 11,500 lawsuits according to the company's most recent tally.
Federal Judge Elden E. Fallon, the judge overseeing the federal Vioxx suits told the lawyers involved in the suits that he wants the parties to meet after the first series of federal trials is over, and gauge where the litigation stands.
(7/8/06)- The New England Journal of Medicine has retracted a part of a paper it had published in 2004 about Merck's pain-killing medication Vioxx. In a correction posted online, the journal said that the paper's abstract-or summary- should no longer claim that Vioxx causes heart damage only when it is used for more than 18 months.
The 18-month claim does remain in a different part of the paper, the results section.
"It's still in both the results and the conclusion of the paper, though with some slightly different wording," said Sandra Jacobs, a spokeswoman for the journal.
Last month, Merck acknowledged that it had previously misreported the results of a crucial statistical test the company had said proved its 18 month theory. Please see out item dated 6/9/06.
(6/14/06)- Carlene R. Lewis, a Houston attorney, who was part of a team of three lawyers that won a $253.5 million verdict against Merck & Co. for its painkilling Cox-2 inhibitor medication Vioxx died in Houston on June 5 at the age of 51.
The cause was complications from ovarian cancer, according to her husband, Greg Lewis.
Mrs. Lewis began investigating the risk of Vioxx in 2000, after a friend of her mother's said she had become ill after taking the medication. Mrs. Lewis wrote two letters to Merck seeking to negotiate a settlement on behalf of her mother's friend, but the company rejected both offers.
Mrs. Lewis was appointed by a federal judge to a panel of lawyers charged with overseeing the gathering of records concerning Vioxx from the company. She also was appointed to a similar panel in connection with litigation against Pfizer, which is also in the Cox-2 inhibitor classification of medication
(6/9/06)- Merck & Co. acknowledged that it had used the wrong statistical data-analysis when it concluded that the increased risk from the usage of Vioxx for cardiovascular events did not occur until the 18th month. The company said that the correction did not change the study's result, but many scientists questioned this statement.
The company used a statistical variable known as the "linear time" when in fact it should have used the "logarithm of time" variable.
The test the company used to check the results shows that there is a 7% chance of Vioxx has an equally high risk of causing heart attacks both before and after the 18-month benchmark it reached. The results of the Approve study were first published in the March 17, 2005 issue of The New England Journal of Medicine.
The company notified the study's authors, the FDA and the New England Journal of Medicine before making the error public
Robert E. Meyer, the office of Drug Evaluation at the FDA's Center for Drug Evaluation and Research, said both the logarithmic and linear statistical methods, for determining whether the pattern of risk for Vioxx is changing over time, are appropriate.
(5/25/06)- The results of the one-year follow-up study of Merck's Approve Vioxx drug trial suggests that the cardiovascular risk associated drug begins within four months after patients begin taking it, rather than the 18 month period of time that the company had concluded.
In a graph accompanying a 107-page summary of the data that the company had prepared, the number of " confirmed thrombotic cardiovascular events" indicates that those occurring in Vioxx patients began to outpace those on a placebo by the fourth month. In a statement accompanying the summary the company denies that the data shows that the risk from the drug starts outpacing the placebo group until the 18th month.
The company did not offer any explanation as to why the graph indicated the earlier time frame for which the risk increased. The company also declined to comment on whether or not the summary had been sent on to the FDA.
At last count more than 11,500 suits had been filed against Merck on behalf of Vioxx patients.
(5/20/06)- The study that was conducted by Merck that showed that Vioxx increased the risk for a cardiovascular event, was a three-year study called Approve. Newly released data from Merck suggests that patients remained at risk for a cardiovascular event during the first year after the patient stopped taking the drug.
The findings for the fourth year alone aren't statistically significant, according to the company since it could be due to chance. The full four year data confirmed a statistically significant 1.74 times higher risk of heart attacks and strokes for the Vioxx patients, compared with patients in the placebo group. After the first three years of the study, patients who had taken Vioxx were 1.92 times as likely to suffer a cardiovascular event.
Not all patients completed the full four-year study. Of the 1,721 patients who could be tracked, 15 of the patients who had taken Vioxx had a cardiovascular event in the fourth year, versus only 9 in the placebo group who had such an event. This 1.85 time increased chance of having such an event is not considered statistically significant.
The risk of ischemic stroke was higher for Vioxx patients versus the placebo group in the fourth year, but there was no statistically significant difference in mortality for the fourth year.
A Vioxx case that was scheduled to begin in state court in Tampa Florida on July 31 has been postponed by the mutual consent of both parties. This case involves a retired soccer player by the name of Refic Kuzic, who suffered a nonfatal heart attack in 2001 after having taken Vioxx for about two and a half months.
The Atlantic City New Jersey state courtroom will be the scene of the next Vioxx trial before Judge Alice Higbee commencing on June 5th. This will be followed on June 21 with the first of the California cases, and will be held in the Los Angeles County courtroom. The federal cases involving the drug are set to resume in Louisiana on July 24th.
Judge Victoria Chaney will preside in the California courtroom, and she was a registered nurse at Cedars Sinai Medical Center in Los Angeles before attending law school. There will be two plaintiffs in this case. The first plaintiff is a 66-year old male who ingested different levels of Vioxx ranging from 12.5 mg to 25 mg over a 26-month period of time prior to his heart attack on September 17, 2001.
The second plaintiff is a 63-year old male who took the drug for a eight month period of time prior to his heart attack on December 29, 2001.
(4/23/06)- Dr. Randall Harris, director of the Center of Molecular Epidemiology at the Ohio State University Medical Center in Columbus, Ohio was the leader of a group of researchers which compared the habits of 323 breast cancer cases to 649 people without the disease. The study concluded that the use of a Cox-2 drug reduced breast cancer risk by 71%, The results of the study were presented at the American Association for Cancer Research in Washington.
The results of two large studies showed that high dosages of the Cox-2 drug Celebrex, taken daily for three years reduced the formation of pre-cancerous growths in the colon.
The only Cox-2 drug now being sold in the United States is Pfizer Inc.'s Celebrex. Merck's Vioxx was pulled from the market in 2004 after it was linked to a higher risk of cardiovascular events and strokes. Pfizer's Bextra was withdrawn in 2005 after reports of a life-threatening skin reaction.
(4/22/06)- The Texas state court jury found for the plaintiff 71-year old Leonel Garza, and awarded $7 million in compensatory damages and $25 million in punitive damages to his family. For more particulars on this case please see the item below dated 1/11/06. The verdict came as no surprise since Starr County in Texas is considered to be a "plaintiff " county. The scoreboard now stands 3 cases in favor of Merck and 3 cases against the company in the Vioxx trials.
Mr. Garza died from a heart attack in 2001, and had been using Vioxx for only about one month. Texas law caps punitive damages, so the amount of that phase of the verdict will be reduced to $7.75 million. Mr. Garza had a long history of heart disease, including a previous heart attack.
Jurors had deliberated for about 8 hours, over 2 days before reaching their 10-2 verdict. The case was held in Rio Grande City, a South Texas town of 13,000, near the Mexican border. The case began in January, but jurors heard testimony for only four days a month because Judge Alex W. Gabert who presided over the court is responsible for cases in several counties.
(4/12/06)- The Atlantic City, NJ jury sitting in the state court has awarded the plaintiff, John McDarby, $9 million in punitive damages in connection with his suit against Merck and its painkiller drug Vioxx. The jury could have awarded him as much as $22 million, since he and his wife had won a verdict of a total of $4.5 million in their personal injury claim against Merck in the earlier phase of the trial. Under N.J. law a plaintiff can be awarded as much as 5 times the amount of the personal injury award in the punitive damage part of the award.
The Atlantic City, NJ jury sitting in the Merck Vioxx cases awarded $3 million to plaintiff McDarby for personal injuries (pain and suffering), and $1.5 million to his wife (for her loss of "society and services of her husband"). The same jury rejected the claim of the plaintiff Cona for his personal injuries. The amount of any punitive damages to be awarded will be determined by the jury, which will hold hearings starting Thursday. In order to win a claim for punitive damages under New Jersey law the plaintiff will have to prove that Merck intentionally misled the FDA.
The jury also ruled that Merck committed consumer fraud in the marketing of the drug by failing to provide adequate warning of the increased risk for cardiovascular events for patients who use the drug for more than 18 months.
Both plaintiffs will be reimbursed for their attorneys' fees and their out-of-pocket costs for Vioxx-a sum that is tripled under New Jersey consumer fraud law. Mr. Cona will receive $135 for his proven Vioxx bill, and Mr. McDarby will receive $11,904 for his proven Vioxx bill. Only a portion of Mr. McDarby's legal fees will be reimbursed under the New Jersey consumer fraud law.
Although the jury found that Merck concealed the risks for cardiovascular events from Cona's doctor, his heart attack was not a substantial factor in causing Cona's heart attack.
Bonnie Zakotnik, the lawyer for Ellis Maximo Diaz, announced that she was dropping his federal lawsuit against Merck the maker of the drug Vioxx, because there was no way she could go through all of the available documents from Merck by June 12, when the federal trial was due to start. She had asked Judge Eldon E. Fallon of the Federal District Court in New Orleans to delay the trial, but he had refused to do so.
Mr. Diaz, a retired medical photographer, had taken Vioxx for19 months before his heart attack in May 2004.
(4/3/06)- Merck & Co. rested its case on Thursday after having called only five witnesses: two company scientists, two cardiologists and plaintiff Cona's psychiatrist. The company's defense was based on the fact that the plaintiffs' physical condition caused their cardiovascular problems not Vioxx. The company also claimed that it acted reasonably in connection with the safety issue for the drug.
Lawyers for Cona and McDarby called 14 witnesses, using data from clinical studies of the drug to show that Merck knew of the high risk factor involved in using the drug for more than 18 months. McDarby's lawyers, Robert Gordon and Jerry Kristal acknowledged the physical ailments of their client, but they emphasized the fact that he would not have taken the drug had he been aware of the increased risk involved for someone in his physical condition.
McDarby's physician testified that he would not have prescribed the drug had he been adequately warned of the risks involved for patients in the physical condition that his patient was in.
Lawyers for all parties to the case will sum-up their cases to the six-woman, two-man jury on Monday. Judge Higbee will then issue her instructions to the jury either on Monday or Tuesday, and the jury will then begin its deliberations.
(3/25/06)- U.S. District Court Judge Eldon E. Fallon of New Orleans, the federal judge who is overseeing the federal Vioxx cases, ruled that the plaintiff lawyers can depose David Graham, an FDA official who has criticized the agency for its handling of the safety issue of the drug. The FDA has traditionally tried to avoid being entangled in civil litigation, and it had denied lawyers requests for Dr. Graham to testify.
When Dr. Graham testified before Congress in connection with the FDA's handling of the Cox-2 drug safety issue, Dr. Graham called Vioxx "a terrible tragedy and a profound regulatory failure." Dr. Graham has been a vocal critic of the FDA's handling of the safety issue for these drugs.
Judge Fallon ruled that the deposition "must proceed because the FDA has acted arbitrarily and capriciously in failing to provide Dr. Graham for a deposition."
(3/14/06)- Dr. John Braun, an internist from Oradell, N.J. testified on behalf of his patient John McDarby that he saw the plaintiff over a dozen times between 1998 and 2003, and prescribed Vioxx for his arthritis, which he said was effective in treating the pain. The doctor further testified that had he known that Vioxx increased Mr. McDarby risk of having a heart attack he would not have prescribed the medication for a man in his condition.
Dr. Braun was not allowed to testify to the fact that he had taken Vioxx himself for nearly two years to treat his own neck pain. He also was not allowed to testify that he himself had suffered a heart attack and was presently suing Merck in connection with the Vioxx matter.
The plaintiff, Thomas Cona, testified that a lot of the Vioxx that he had used, had been given to him by his physician, who had received a lot of the pills as samples from the Merck salesman. He also testified that he had not been entirely truthful in his pretrial depositions.
(3/9/06)- The first trial for Pfizer's Cox-2 inhibitor drug Celebrex has been set for June 6 in an Alabama state court. Celebrex is the only Cox-2 inhibitor rheumatoid arthritis drug that is still on sale in this country. Pfizer put a "black-box" warning, on the label for the drug upon the recommendation of the FDA in August 2005.
The label warns that the drug may increase the risk of cardiovascular events, including heart attack and stoke. Total sales of Celebrex dropped in 2005 by 48% to $1.73 billion according to the sales figures from Pfizer.
The plaintiff in the Alabama case is Rosie Ware, of Barbour County, Alabama who was 53 years of age at the time of her stroke. She is being represented in the case by the law firm of Beasley, Allen, Crow, Methvin, Portis & Miles PC of Montgomery, Alabama, which was the law firm that represented the plaintiff in the losing first federal trial of Merck's Vioxx.
Ms. Ware's attorney in the case is Jere Beasley who said his client was a healthy, non-smoker who took Celebrex for a back pain that she was suffering from, who was left disable after suffering the stroke.
There are more than 200 federal cases pending over Pfizer's two pain -iller drugs Celebrex and Bextra that have been consolidated before Judge Charles R. Breyer of the U.S. District Court for the Northern District of California. Bextra was pulled from the market by Pfizer in April of 2005
The next of the Merck Vioxx trials started on Monday, February 27th in state court in Atlantic City, N.J. before New Jersey Superior Court Judge Carol E. Higbee. The trial will combine the cases of two plaintiffs at the same time, both of whom had taken Vioxx for more than an 18 month period of time.
In this trial the plaintiffs' attorneys will try to convince the jury of Merck's liability because the company failed to properly warn users of Vioxx of the increased risk of heart attack and/or stroke.
Mark Lanier will represent one of the plaintiffs in this trial. He is the same attorney who represented the plaintiff in the only case that Merck has lost at a trial in the Vioxx matter in a Texas state court proceeding. His client in this particular case is Thomas Cona, who survived a heart attack in 2003 after allegedly taking Vioxx for 20 months for back pain. Mr. Cona was 57 years old at the time of the heart attack, overweight and had high blood pressure and high cholesterol readings. Although conceding those points, Mr. Lanier will point out the fact that the Vioxx label had no warnings about the risk of the drug, even though Merck knew that it increased the risk of heart events for users of the drug.
The other plaintiff is John McDarby, 77, who is represented by Robert J. Gordon. Mr. McDarby is a diabetic, who his attorney will argue, never would have taken Vioxx for his rheumatoid arthritis had the label properly warned him of the risks he was subjecting himself to in taking the drug.
Christy D. Jones is Merck's lead lawyer in the case.
The New England Journal of Medicine published a letter written by 11 scientists who were co-authors involved in the article on Vioxx that was published in the journal in November 2000. The letter reiterated their previous stance and its conclusions about the drug. Merck did not employ these scientists, but Merck did finance the study. Two Merck scientists who were also co-authors of the original study wrote a separate letter that was also published by the journal reiterating their original conclusions.
Dr. Claire Bombardier, a Toronto rheumatologist was the lead outside author on the original study. The journal's editors also pointed out the fact that the study used an earlier closing date for evaluating the cardiovascular risk of the drug than they did for the gastrointestinal risk. Because of that fact they were able to exclude 3 deaths that took place among the Vioxx users, while using a one month later date for comparative purposes for the gastrointestinal comparison with naproxen, which is better known by its trade name of Aleve.
The journal's editors however also reaffirmed their earlier complaint, saying that the article, "did not accurately reflect the potential for serious cardiovascular toxicity with Vioxx."
According to an article in The Nutrition Business Journal, Americans spent $734 million on glucosamine and chondroitin in 2004, making them two of the most widely used dietary supplements in this country. A large federal study has determined that the supplements are being used to alleviate arthritic pain, the money in effect is being wasted.
The study enrolled 1,583 patients with osteoarthritis of the knee who were randomly assigned to one of five groups for a 24-week period of time. Some of the patients took glucosamine, some took chondroitin and some took both. The rest of the patients in the study were either given a placebo, or celecoxib, which is also known as Celebrex.
No statistical improvement was found in those patients who took the glucosamine, chondroitin, or combination of the two. The patients who took the celecoxib were found to have had a statistically significant improvement in their symptoms. Dr. Daniel E. Clegg, a researcher at the University of Utah School of Medicine was the lead author of the study. Dr. Clegg cautioned that addition studies would have to be conducted before the effectiveness of glucosamine and chondroitin could be finalized.
The study was financed by the National Center for Complementary and Alternative Medicine and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Glucosamine and chondroitin are substances found naturally in our joints. Glucosamine is a modifiend sugar that is thought to play a role in the formation and repair of cartilage. Chondrotin is part of a large protein, proteoglycan, that provides elasticity to cartilage.
Dr. Stephen E. Strauss, director of the Alternative Medicine and the National Institute of Arthritis and Musculoskeletal and Skin Diseases, a sponsor of the study, said a national survey in 2002 found that about 5.2 million Americans had used one or both supplements in the preceding year. Veterinarians prescribe glucosamine and chondroitin for treatment of pets with arthritis.
(2/20/06)- The federal jury sitting in New Orleans in the retrial of the Irvin-Vioxx case decided that the drug, which is manufactured by Merck was not responsible for his death. See our note below dated 2/5/06 for more information in connection with the earlier trial. Richard Irvin was a 53-year-old Florida resident who had suffered a fatal heart attack about one month after he began taking Vioxx.
The earlier federal trial, which was the first Vioxx case that was tried in the federal court system resulted in a hung jury. Mr. Irvin's widow, Evelyn Irvin Plunkett, and two of his children testified that Mr. Irvin's health had been excellent up to his heart attack.
Andy Birchfield, a lawyer for Ms. Plunkett, said that the ruling by U.S.District Court Judge Eldon Fallon, that two of the plaintiffs' experts- a cardiologist and a pathologist- could not testify that Vioxx was the cause of the death, because they were not experts about Vioxx was the key reason for the plaintiff's losing the case.
The jury deliberated for 3 hours and 40 minutes, the shortest period of any jury in the Vioxx cases.
Dr. Richard Schirmer, who was Mr. Irvin's son-in-law, was an emergency room physician in another city who had prescribed the medication for him. Dr. Schirmer testified that he would not have prescribed the medication for his father-in-law had there been a warning on the drug label of the risk of heart attack.
(2/05/06)- The federal retrial of the Evelyn Irvin Plunkett, the widow of Richard Irvin vs Merck over Vioxx will begin in New Orleans on Monday February 6 before U.S.District Court Judge Eldon Fallon. The retrial is necessary because the first trial, which was held in Houston because of the flooding in New Orleans as a result of hurricane Katrina, ended in a hung jury, with 7 of the jurors favoring Merck and 1 favoring the plaintiff. A jury of 5 males and 3 males was empanelled to hear the case.
The second and third federal Vioxx trials which were scheduled to start in March and April, before Judge Fallon have been postponed for about two months. The second case involves Ellis Diaz, who was considered a medium-term user of Vioxx. His case was originally set to start on March 13, but it has been delayed until sometime in May, because according to his attorney Bonnie Zakotnik, the medical records of his doctor were damaged by the flooding that resulted from Katrina.
The third case that is scheduled to be heard in the federal court is that of Charles Borowicz, who according to his attorney used Vioxx for more than 18 months. This case was originally filed in state court in Atlantic County, NJ, but was refiled as a federal case in New Orleans.
Judge Fallon instructed both the Plaintiffs Steering Committee and Merck to each submit a list of five Louisiana cases for subsequent trials. Each side will be able to strike two cases from the other's list, leaving 6 cases "in queue". This in turn means that each side can formally ask the other side about evidence and witnesses that they may be using in connection with the impending trials.
In a conference call after announcing its fourth quarter earnings, Merck revealed that it is now facing about 9,650 product liability lawsuits, including approximately 19,100 plaintiff groups, which is an increase of 450 cases since its last update on December 15. It also announced that it was increasing its reserves by $295 million for future Vioxx legal costs (the reserve was $685 million as of December 31), which the company believes will be spent through 2007. The company spent $285 million in aggregate on worldwide Vioxx legal expenses in 2005.
(2/1/06)- We at therubins would like to apologize to our viewers for reporting in our item date 1/31/06 that the judge in the Garza Texas lawsuit had dismissed the plaintiff's action against Merck and the two physicians who had been treating him at the time of his death. We were mistaken in that report because that lawsuit is still continuing in the Starr County, Texas courthouse.
On the other hand Judge Carol E. Higbee of Superior Court in Atlantic City N.J. granted Merck's motion for summary judgment, say that Edgar Lee Boyd, was unable to show he was hurt by Vioxx or by the company's alleged failure to warn of side effects.
So far the scoreboard reads: one victory for the plaintiff (in a Texas state court); one for Merck (in a New Jersey state court) and a mistrial (in a federal trial in which the jury had voted 8-1 in Merck's favor) in the Vioxx trials.
(1/11/06)-The Garza trial has been set to commence in state court in Texas, and as such it will become the fourth of the Vioxx cases to go to trial. This case was briefly part of a set of federal cases consolidated in the court of U.S. District Court Judge Eldon E. Fallon of the Eastern District of Louisiana, but it was sent back to Texas state court in November.
The Garza case was originally set to start in February 2005, but had been stalled for months. The trial will take place in Starr County, Texas, a rural border county. Lionel Garza was a 71-year old male with a history of heart problems. He died of a heart attack only one month after starting Vioxx. Mr. Garza had a heart attack and had undergone an angioplasty to open clogged arteries months before his fatal heart attack in April 2001.
According to Mr. Garza's co-lead attorney Jose Escobedo Jr, the plaintiff had a scan that showed normal blood flow to the area where the fatal clots occurred, and his doctors wrote in medical records that he was "stable."
The next cases that are set to go to trial in the Vioxx matter after the Garza case, will take place in state court in New Jersey. The two plaintiffs in this lawsuit were taking Vioxx for more than 18 months before the events occurred that forms the basis of the suit. Please see our item dated 1/4/06 below.
(1/4/06)- The next Vioxx case court trial is set for February 27, 2006 in state court in New Jersey. It will be a consolidated action with two plaintiffs. The McDarby and Cona consolidated trial will be heard in front of New Jersey Superior Court Judge Carol E. Higbee.
John McDarby suffered a heart attack after using 25-mg of Vioxx for approximately 49months. He is 75-years of age and suffered from Type 2 diabetes. He did not have high blood pressure or high cholesterol. He did not smoke nor was he obese. He used to be quite active physically but he is now confined to a wheel chair after fracturing his hip after falling due to a myocardial infarction.
According to the figures in Merck's latest 10Q filing, there are now 18,250 plaintiff groups suing on the Vioxx matter up from the 11,700 plaintiffs groups in its previous 10Q filing. That same new 10Q document shows that there are now 9,200 lawsuits filed versus the 6,400 lawsuits filed in the previous 10Q filing.
Pfizer Inc. has agreed to finance a study that will be undertaken at the Cleveland Clinic, led by Dr. Steven E. Nissen, a cardiologist at the clinic as to the safety of Celebrex in high-risk patients. Dr. Nissen has been one of the loudest critics as to the safety of cox-2 painkillers. The study will enroll as many as 20,000 patients and will begin next year. It could cost as much as $100 million to run before it is completed. Celebrex had $1.26 billion in sales for the first nine months of this year according to Pfizer.
Patients in the study will have some form of arthritis along with histories including a previous heart attack, stroke, angina, coronary bypass surgery or stent procedures. Others will have diabetes, a known risk factor for cardiovascular disease. Those enrolled in the study will be followed for a two-year period of time.
One-third of the patients will be given Celebrex; one-third Motrin, or ibuprofen; and one-third will receive Aleve or Naprosyn, both brand names for naproxen. The study will end when about 700 of the patients have died or had a heart attack or stroke, thenumber expected in such a high-risk group even without painkiller treatment.
(12/14/05)- After deliberating for a total of about 18 hours on Thursday, Friday and Saturday, the jurors in the Irvin case, which was the first case to go to a federal trial on the Merck-Vioxx matter could not reach a unanimous verdict. Unlike state court civil trials, federal civil court trials require a unanimous verdict. The nine-member panel had voted 8-1 in favor or Merck, after an initial vote of 7-2 in favor of Merck. The judge therefore declared a mistrial, and will set a date for a retrial to take place early in 2006
U.S. District Court Judge Eldon E. Fallon of the Eastern District of Louisiana, who presided over the two week trial in Houston will set a new trial date sometime in February, at which time the New Orleans court system is expected to be fully operational. As of September 30, there were about 2,900 federal lawsuits pending. Judge Fallon will set additional trial dates for some of the other cases in February, March and April.
Carol E. Hughes, the New Jersey state court judge overseeing the Vioxx trials in that state has asked both sides to prepare to try two lawsuits in a consolidated trial that is expected to start February 27, a proposal that Merck opposes. The next trials in New Jersey will involve plaintiffs who had been taking Vioxx for longer than 18 months.
(12/10/05)- U.S. District Court Judge Eldon E. Fallon of the Eastern District of Louisiana has delivered on his promise to have the Irvin case jury decide the case within two weeks after the trial began. The court, which is sitting in Houston, because of the flood from hurricane Katrina, had a curve ball thrown at it by the plaintiff's lawyers, in the form a motion to declare a mistrial that may delay the decision.
The reason for the motion arose as a result of an editorial in the New England Journal of Medicine entitled "Expression of Concern". The editorial cited "inaccuracies and deletions" in Merck's Vigor study the results of which were published in the Journal in November 2000. Although the study stated that 17 patients who were taking Vioxx had heart attacks, in fact 20 patients had heart attacks. Merck claimed that these 3 heart attacks occurred after the study had ended, but the Journal asserted that this was untrue.
The Vigor study began in early 1999 and was paid for by Merck. The study was intended to look at gastrointestinal problems such as internal bleeding and ulcers that arose as a result of taking this Cox-II medication compared to the painkiller naproxen, which is sold under the brand name of Aleve. The study was not officially designed to look at the issue of heart attack comparisons, but only 4 of the naproxen patients suffered heart events compared to the 17 Vioxx users who suffered heart attacks.
Gregory Curfman, executive editor of the Journal said that all three of the new cases came from the group of supposed lower cardiac risk patients. Merck said that the data about the heart attacks was provided to the FDA, presented to an FDA advisory panel, disclosed to physicians, and included in news releases later issued by the company. Merck further asserted that the three additional heart attacks "did not materially change" the conclusions of the study.
The jury of five men and four women will have to answer 12 questions about the roles of Merck, the son-in-law emergency room doctor who prescribed the Vioxx to Mr. Irvin, the physical condition of Mr. Irvin himself and the dangers posed by the medication. If Merck is found liable, jurors will have to consider what would be fair compensation to Mr. Irvin's children and widow for the suffering and the loss of his income and companionship.
(12/8/05)- U.S. District Court Judge Eldon E. Fallon of the Eastern District of Louisiana, who is presiding over the "third" Vioxx trial in Houston, Texas has ruled that the plaintiff in the case can introduce evidence showing that Merck knew of the short term risks involved with the usage of Vioxx as well as the longer term usage of the drug. This is the first Vioxx trial being held in the federal court, since both earlier trials involved the state court of Texas and New Jersey. The case has been moved to Houston because of the flood that resulted from hurricane Katrina in New Orleans.
Earlier evidence has shown that usage of Vioxx over an 18 months period of time increased the risk of heart attacks and strokes. In the Houston case lawyers for Evelyn Irvin Plunkett will argue that Merck is responsible for the death of her then husband Richard Irvin, even though he used the drug only for 24 days before his death.
Judge Fallon denied Merck's request at a pretrial hearing to limit testimony about Vioxx's short-term risks. Plaintiff's attorneys plan to introduce evidence showing that Merck knew of the short term risk of the drug through internal memos from its own scientific staff. By his ruling, in effect it means that all the pending federal cases can introduce evidence of the short term risk of Vioxx, as well as its longer term risk.
If Merck were to lose the so called "stronger cases" involving short term risk of the drug, the company would be in a much weakened position in defending itself against the longer term usage cases. If they win the short term cases, it does not improve their chance of winning the longer term usage cases.
Judge Fallon stated that he hopes to conclude the case within a 2 week period of time, even if it means holding court sessions in the evening and on weekends.
(11/21/05)- New Jersey Superior Court Judge Carol E. Higbee, the judge who is overseeing the Vioxx cases in New Jersey announced that she would select the next case that would go to trial in that state on November 28. The trial will begin on January 30, 2006. There are at last count 3,254 cases pending in New Jersey in the Vioxx matter.
The judge will make her selection from one of seven cases that have been selected by plaintiff and defendant attorneys as the potential next eligible case. All of the seven potential cases involve patients who were taking the drug for longer than 18 months. One of the seven potential cases involves a plaintiff who has died. Of the cases filed in New Jersey, plaintiffs' attorney say some 61% involve patients that are believed to have been taking the drug for 18 months or longer.
(11/08/05)-There are still about 2,750 Vioxx lawsuits pending against Merck in the state courts of New Jersey, which is Merck's home state, and a total of about 6,400 actions pending in the Vioxx matter throughout the court systems of this country. The next case to go to trial in this matter will be in the federal court in Houston on November 29. Incidentally, this case originally was scheduled for the federal court in New Orleans, but because of the hurricane and flood it has been moved to Houston.
Many legal experts feel that the next case is one of the weakest cases against Merck of the many that are still pending. In the Houston case, Evelyn Irvin Plunkett is suing Merck after her husband, Richard Irvin, 53 died of a heart attack 24 days after beginning to take Vioxx. Mr. Irvin was an emergency medical technician who died in May 2001. Andy Birchfield will represent the plaintiff in this action. Phil Beck, a prominent trial lawyer, will lead Merck's defense team in this case..
According to court filings by Merck, Mr. Irvin had high blood pressure and high cholesterol levels. His autopsy showed that he had "advanced heart disease." Merck is seeking to have its marketing material excluded at this trial, because Mr. Irvin did not get his prescription for the drug from a doctor who had received such material from Merck. He got the prescription from his son-in-law, an emergency room physician who had not been visited by any Merck sales people.
You may be wondering how it is determined as to which case proceeds to trial first in these Vioxx matters. The next trial in New Jersey is set for a trial date of January 7 before Judge Carol Higbee, who presided over the Humeston case. The determination as to which case should be next is set under an agreed upon agenda for determining the order of trial plaintiffs. W. Mark Lanier, the plaintiff's attorney who won the Texas case against Merck will be the lead attorney in this case.
A plaintiff's steering committee and Merck each provide a list of five cases they would like to try next. Each side can strike three of the cases selected by the other side. This procedure is for the state of New Jersey only, and Judge Higbee has indicated that she may at some point soon send some of the cases to other judges in the state.
There were two questions that were decided by the jury in the Humeston case in New Jersey. On the first question the jury of 3 men and 6 women voted 8-1 that Merck either did not know that Vioxx carried cardiovascular risks at the time that it was prescribed for Mr. Humeston in 2001, or that the company adequately warned physicians about those risks.
On the second question the jury voted that Vioxx had not violated consumer fraud rules and did not use "unconscionable practices" in marketing the drug to physicians.
Incidentally Merck and federal officials are discussing the possibility of returning Vioxx to the marketplace, although it will be many months before that matter is finalized.
(11/4/05)- After a seven-week trial, it only took eight hours of deliberation by a New Jersey state court jury to find for the defendant in the second of the so-called "Vioxx trials". Unlike the first trial in the state court in Texas which found for the plaintiff and against Merck the New Jersey decision represented a complete victory for Merck. The next case in the "Vioxx trials" now moves on to the federal court in Houston, with the scheduled starting date for the trial being November 28.
In the New Jersey case, the plaintiff Humeston allegedly took the drug Vioxx for only a two-month period of time in 2001. The plaintiff who is now 61 years of age, was overweight, had a family history of heart problems and was under a great deal of stress in connection with his job. The attorneys for Merck questioned whether or not Mr. Humeston took the drug for even the two months that was alleged in the complaint.
Merck was cleared of the allegation that it failed to warn consumers about the drug's risk and engaged in "unconscionable commercial practices." Most legal experts believed that the case was a weak one to begin with, and that the facts of this particular case were in Merck's favor. Merck voluntarily removed Vioxx from the market in September 2004.
The greatest increased risk for having a heart attack after taking Vioxx seems to be for those who took the drug for more than an 18-month period of time
(9/22/05)- The FDA has turned down for approval Pfizer Inc.'s injectable pain reliever called Dynastat, a member of the Cox-2 class of drugs. The drug had been developed by Pharmacia Corp., which was taken over by Pfizer in 2003. The FDA had first turned down the drug for approval in 2001, but Pfizer had submitted additional data, which the company hoped, would cause the FDA to change its mind.
Dynstat, known generically as parecoxib, is sold in many countries, including those in the European Union, for the short-term treatment of surgical pain in hospitalized patients. Some studies have shown that the drug can reduce patients' need for narcotic medications for pain. The drug is converted by the body into Bextra, or valdecoxib, after injection. Pfizer had withdrawn Bextra from the market at the request of the FDA in April.
(8/29/05)- The following item came from the Dow Jones News tape:- The "Therapeutic Products Directorate (TPD), the
Canadian federal authority that regulates pharmaceutical drugs and medical
devices for human use, released a report of the Expert Advisory Panel on the
Safety of Cox-2 inhibitors. The panel ruled unanimously (vote: 13 vs 0) that
Pfizer's Celebrex should continue to remain on the market in Canada and Merck's
Vioxx be reintroduced to the market (vote: 12 vs 1). However, the panel voted
eight to five that Bextra not be allowed back on the market, indicating CV risk
and rare skin disorders outweigh potential benefits of the drug.
The reasons cited for keeping Celebrex and Vioxx on the market include 1) the increased risk of CV disease appears similar to that of most NSAIDs, 2) GI risk appears less than most NSAIDs, and 3) benefits from having a variety of drugs available for pain relief. With Bextra, the panel felt that potential rare skin disorders and CV risks associated with Bextra outweighed the benefits received from the drug. As a reminder, in Febrary 2005, the FDA Advisory Panel ruled 17:15 in favor of MRK's Vioxx to be sold in the U.S."
(8/20/05)- A Texas jury awarded Carol Ernst, the widow of Robert Ernst $24.5 million for mental anguish and economic losses and $229 in punitive damages in the first case tried and decided against Merck's Cox-2 pain inhibitor drug Vioxx. The case was tried in a state court in Brazoria County, Texas.
Texas law caps punitive damages so that part of the award will be limited to $1.6 million, meaning the overall award would not exceed $26.1 million.
Merck announced that it would appeal the decision. The company said that the court made several erroneous rulings that will form the basis for its appeal. Included in its early indication as grounds for the appeal are the following:
(5/21/05)- With all the adverse publicity that the Cox-2 drugs (Vioxx, Bextra, and Celebrex) have had in the last few months, acetaminophen seems to be developing the lead in regard to being a good alternative for the relief of chronic pain. Acetaminophen, which is often referred to by its most popular brand name as Tylenol has no anti-inflammatory action, as do the NSAIDs.
Ibuprofen (Advil, Motrin1B) and naproxen (Aleve) are better than aspirin in dealing with painful inflammations and have less risk of gastrointestinal bleeding but there is an increased risk of ulcers developing through long term usage. When taking everything into consideration acetaminophen is a safe drug for both children and adults.
Taking more than 4,000 milligrams a day of acetominophen on a chronic basis can however damage the liver of the user. With the higher-dose tablets now being sold to treat arthritis, exceeding the 4,000 milligram a day limitation can be done easily unless the user keeps a good record as to exactly how much of the drug is being consumed. Follow the instructions on the bottle carefully to take 2 tablets every 8 hours with a maximum daily dose of 6 tablets in a 24 hour period. Keep in mind also that acetominophen and alcohol do not mix well.
(4/11/05)-Citing the increased risk for a rare dangerous skin disease, as well as the increased risk for heart attacks and strokes, the FDA went against the vote of its safety panel's vote, and required Pfizer to remove its Cox-2 inhibitor drug Bextra from sale to the public. At the same time it called for "black box" warning of increased cardiovascular and gastrointestinal risk labeling on all prescription versions of nonsteroidal anti-inflammatory drugs including Mobic, Naprosyn, Voltaren and more than 12 similar drugs.
The agency also wants to include warnings on over-the-counter painkillers such as Advil, ibuprofen, Aleve and naproxin. Neither acetaminophen sold as Tylenol, and other names, nor aspirin are affected by the warnings. Tylenol can damage the liver and aspirin can hurt the stomach and increases the risk of bleeding for those with stomach ulcers.
No final decision was arrived at concerning Merck's Cox-2 drug Vioxx, which the company voluntarily removed from the market in September 2004. Merck has stated that it may resume sales of the drug, but the FDA has said that an advisory committee would review any such application. Pfizer has agreed to undertake a large study of Celebrex's effects on the heart. Pfizer has suspended all advertisements for Celebrex, but the FDA stated that it is powerless to require a company to stop advertising a drug that it has previously given approval to be marketed.
As a result of this ruling there are two Cox-2 drugs that could face a much tougher road ahead before they can gain approval from the FDA to be sold in this country. They are Merck's Arcoxia, which is sold in 54 countries outside the U.S., and Novaritis AG's Prexage. Both companies said that they stood behind the safety of their respective drugs.
The federal court handling the Vioxx and Bextra cases has assigned them to the federal court in New Orleans as consolidated actions to be heard by Judge Stanley Duval and Judge Eldon E. Fallon.
(2/20/05)-The results of the three day review of the safety of the COX-2 drugs by an FDA panel are in. Pfizer's Celebrex (only 1 panelist dissented) and Bextra (by a vote of 17-13 with 2 abstentions) both won votes of approval for their safety by the panel. In a surprise vote, by a close margin (17 for-15 against) Merck's Vioxx won the safety panel's approval. Stricter warning labels will have to be added for each of the drugs.
Merck will have to submit additional data to the FDA before it can resume selling Vioxx, which it had voluntarily removed from the market in September 2004. The panel also recommended that these drugs should not be allowed to be advertised directly-to-the consumer. The FDA usually accepts the panel's recommendations.
Dr. Alastair Wood, the panel's chairman, said after the meeting that, "I think physicians need to be more thoughtful about how they use these drugs in the future." He went on to further state, "My sense is that to put it bluntly naproxen is better for you than the" other pain pills. "Most patients should probably start on naproxen," perhaps together with a drug like Prilosec taken to reduce the risk of ulcers.
Panel members largely concluded that naproxen is the safest pain reliever. Sales of the pain medication Aleve should benefit the most from this comment. In December, researchers had suggested that a large study showed that Aleve increased the risk of heart attack. Dr.Constantine Lyketsos of Johns Hopkins Hospital, who helped to oversee the study explained to the panel that an administrative problem, not the increased risk of coronary events is what caused a halt in the study.
(2/15/05)-The FDA hearing as to the safety issues involved with the COX-2 inhibitors will start on February 16 and last through the 19th. Previously undisclosed Merck documents show that the external committee that was monitoring the Vioxx's safety in the clinical trial had early data suggesting that patients taking the drug were at an increased risk of having a heart attack or stroke. Minutes from the first committee meeting in 2000 showed that there were warning signals for patients after being on Vioxx for only four months.
The committee overseeing the safety of the drug consisted of five members. One of the five was an employee of Merck and two of the doctors on the panel had done consulting work for Merck. One of the consultants was the lead author on a paper written with Merck scientists that defended Vioxx's safety and criticized a study that raised issues about the safety of the drug.
The trial was intended to show whether or not Vioxx had any beneficial effects in the treatment of colon polyps. The records show that the drug did have some beneficial results in regards to the treatment of the colon polyps, but the evidence against the safety of the drug in regards to the heart attack and stroke issue continued to pile up.
Merck said that of the 1,287 patients who took Vioxx, 45 of them experienced a heart attack or stroke, compared to only 25 patients out of 1,299 taking placebos. The trial known as Approve began in January 2000. The trial lead researcher was John Baron, a professor of medicine at Dartmouth Medical School. Minutes from that first meeting showed that some members of the panel raised the safety issue about the drug.
At its last meeting on September 17, 2004 the committee members noted that the trend for heart attack or stroke showed increasing risk for a patient having an event were growing sharply with the passage of time. The minutes note that in May 2003 committee data showed a 20% higher chance of an adverse event in the Vioxx patients. The risk grew steadily to an 80% higher risk in February 2004 and 120% in September 2004.
(2/9/05)-Pfizer Inc. has sent a letter to the FDA in which it defends itself against allegations that it did not disclose the finding of increased risk for heart attack or stroke among patients who took Celebrex during a trial of the drug with patients who had Alzheimer's disease. In the letter the company said that the results of the study were submitted to the FDA in June 2001. The company also stated that the results of the study were presented in an abstract at an international Alzheimer's conference in Stockholm in April 2000.
The data was not published and first became available last month when the company posted a synopsis of the study in an online registry for clinical trials. The consumer-advocacy group Public Citizen's analysis concluded that the results of the study showed that Celebrex increased the risk of heart attack or stroke almost fourfold. Pfizer's letter to the FDA claimed that Public Citizen's analysis was statistically flawed and inconsistent with the findings of the safety monitoring board that was overseeing the study.
(1/30/05)- Kaiser Permanente, one of the nation's largest managed care organizations, announced that it has ordered its pharmacies to cease dispensing Pfizer's pain medication Bextra, but would allow them to continue to dispense Pfizer's Celebrex pain killer medication. The suspension of Bextra is the first case of Kaiser's doctors deciding to ban use of a drug that has been approved by the FDA. Kaiser has a membership of over 9 million people throughout the U.S.
Pfizer has previously acknowledged that studies had shown that Bextra increases the risk of heart attack or stroke for patients have had coronary artery bypass surgery. It continues to defend its other COX-2 inhibitor Celebrex as being safe. The FDA will hold a 3-day public hearing to assess the safety of the COX-2 inhibitor drugs starting February 16th. Among the drugs to be highlighted at the hearing are Merck's Vioxx, which has been withdrawn from the market and Pfizer's Bextra and Celebrex. Bayer AG's non-prescription drug Aleve will also come under the scrutiny if the panel.
Bextra had sales of $1.29 billion in 2004, but its sales have fallen off sharply since the COX-2 safety issue has come to the forefront.
AstraZeneca PLC said that the death of a patient taking its cholesterol-lowering medication Crestor was likely to have been caused by an infection unrelated to treatment with the drug. There was some doubt that had been expressed earlier that the death might have been caused by the patient's usage of Crestor.
(1/17/05)-The Senate Finance Committee, chaired by Senator Charles Grassley (R.-Io.) was in the limelight recently when it held public hearings in mid November in connection with its probe of the withdrawal of Merck's pain killing medication Vioxx. It is not the panel responsible for oversights by the FDA. The newly elected Republican Senator from Wyoming, Mike Enzi, chairs the committee that covers this area namely the Senate Health, Labor, Education and Pension Committee. Senator Enzi is a former accountant and shoe storeowner, who has not stated his position on the safety issues involved in the Vioxx-FDA matter.
Senator Grassley will continue his probe of Vioxx and has called for reports from Congress's investigative are, the Government Accountability Office on FDA oversight. The FDA has appointed a panel to report back to it in February in connection with the issue of the safety of COX-2 medications.
AstraZeneca said that it had reported to regulators that a death of a patient taking it cholesterol-lowering medication Crestor was possible. The death possibly caused by rhabdomyolysis, a severe muscle-wasting condition is the same problem that caused Bayer to withdraw its cholesterol lowering drug Baycol several years ago.
A study involving more than 8,000 people that was funded by the National Institutes of Health, Merck and Pfizer found that Vioxx was almost three times as likely to be associated with a nonfatal first heart attack as Celebrex. Scientists at the University of Pennsylvania did the research, and it seems to suggest that not all COX-2 inhibitors are the same.
The study involved more than 1,700 patients, aged 40 years to 75 years old, who suffered a first heart attack that did not kill them between May 1998 and December 2002. A comparison group of 6,800 patients was culled from the same five counties where these people lived.
Vioxx users had a 16% higher risk of nonfatal heart attacks than nonusers. In the Celebrex group however users had a 57% lower risk of heart attack. In the final analysis, the odds of a Vioxx user having a heart attack was 2.72 times higher than a Celebrex user
(12/25/04)-According to doctors and officials connected to the NIH study of the effect of Aleve on Alzheimer's disease, the reason why the study was halted was because the patients involved in the study refused to take their medications when the news about Celebrex became public. Since the patients did not know whether they were getting Celebrex, Aleve or the placebo, they stopped taking whichever one they were receiving.
Initially the data on the risk from taking Aleve was so small that the researchers noted the increased risk with very little alarm. John Breitner, a researcher at the University of Washington, Seattle, headed the study in question. Mr. Breitner stated: "There was a tremendous degree of public panic." In an interview Mr. Breitner went on to say that evidence of naproxen side effects in the study was "not really" statistically significant. Among those patients taking naproxen or the placebo, there were only two or three deaths from heart attack and none from strokes.
For those of you who are taking ibuprofen as a pain medication, most medical experts feel that this medication blocks the heart benefits of taking aspirin
The European Medicines Agency (EMEA) announced that it would expedite its safety review of the COX-2 inhibitors. In making the announcement the EMEA cited data that indicated "an increased risk of serious cardiovascular events" that may be related to the dose and duration of the treatment with Celebrex. This agency expects to hold its hearing as to the safety of the drugs in January as opposed to the February date set by the FDA.
The FDA has recommended that doctors limit prescriptions for Celebrex and Bextra, but at the same time did not ban prescriptions for these drugs entirely. The agency said that the doctors should use their best judgment in prescribing the drugs in light of the recent publicity given to the studies that involved these drugs. It even included keeping patients who were at high risk of gastrointestinal bleeding or had done poorly on other pain pills may still be appropriate candidates for Celebrex or Bextra.
On the other hand the Medicines and Healthcare Products Regulatory Agency in England advised doctors to switch arthritic patients with heart disease to other medications "as soon as is convenient."
(12/22/04)- The FDA issued a warning as a result of an NIH study of patients involved in an Alzheimer's disease study showing an increased risk of heart attacks or strokes as a result of taking the naproxen Aleve. Bayer makes the drug. The FDA's warning was for those taking a dosages greater than 220-mg a day for over 10-days in a row. Those who have taken Aleve in these amounts should consult their physicians.
Naproxen is not a COX-2 inhibitor, but falls within that class of drugs called non-steroidal anti-inflammatories(Nsaids). It began being sold in the U.S. in 1976. The NIH study in question involved approximately 2,400 Alzheimer's patients who had taken Celebrex, naproxen or placebo for as long as 3 years. The patients taking the naproxen had a 50% higher rate of cardiovascular events than those taking the placebo. Those on Celebrex had just about the same rate of adverse heart events as did the placebo group.
The entire group had 70 patients who had heart attacks or strokes, but the researchers did not reveal a breakdown of how many occurred in each group. The patients taking the naproxen got 220-mg dosages twice a day, while those on Celebrex got 200-mg dosages twice a day. There were a total of 23 patients who had fatal heart attacks, but the death rate for each group was not revealed.
(12/20/04)- Another cloud has now been thrown over Pfizer Inc.'s best selling rheumatoid arthritis and osteoarthritis pain medication Celebrex. A safety committee that was monitoring one of two five year drug trials of Celebrex found from preliminary data that the patients who were taking high dosages of the drug were undergoing increased risks of heart problems or strokes.
The study in question is one of about 40 studies undertaken by the National Cancer Institute (NCI) that are exploring whether or not there are some drugs that can prevent colon polyps or colorectal cancer. More than 2,000 patients were split into 3 groups. Group one was given 200-mgs of Celebrex twice a day. Group two was given 400-mgs of Celebrex twice a day, while Group 3 was given a placebo.
A data-safety monitoring committee in looking at the interim data after 33 months found that those given the 800-mgs a day dosage had 3.4 times greater risk of heart attacks and strokes than those on the placebo. The group that had been given the 400-mgs a day dosage had 2.5 times greater risk of cardiovascular events than those on the placebo.
In actual numbers there were 6 cardiovascular events in the placebo group; 15 such events in the 400-mgs a day dosage group and 20 events in the 800-mgs a day group. The problem has led the NCI to terminate the study. Another study sponsored by Pfizer that used the 400-mg dosage for patients did not show a similar problem. Pfizer announced that, unlike Merck with its COX-2 inhibitor drug Vioxx that halted sales of its drug, it would continue to sell Celebrex since it could not explain the different results ensuing from these two trials.
Celebrex is expected to be used by about 26 million patients worldwide this year, with estimated sales coming in at about $3.3 billion for 2004. Last year 21 million prescriptions were written for the drug.
Dr. Lester Crawford, the FDA's acting commissioner said that doctors should consider switching patients who are taking Celebrex to other pain medications such as Advil, ibuprofen or aspirin. Abbott Labs is marketing the prescription pain killer Mobic in this country for the German drug company Boehringer Ingelheim, though this drug is very similar to ibuprofen, which is an over-the-counter medication.
In referring to treatment for pain, Dr. Jonathan Kay, an associate clinical professor of medicine at Harvard Medical School said: "It behooves us to provide our patients with the safest and most effective therapies possible, which at the moment seems not be Vioxx, Bextra or Celebrex. Some of the earlier studies had shown that Celebrex often cause irregular heartbeat or arrhythmia problems.
Celebrex belongs to a widely used class of drugs called Nsaids (non-steroidal anti-inflammatory). The class includes aspirin, ibuprofen, Motrin, Advil and the naproxen drugs Aleve and Naprsyn. Some previous research has indicated that aspirin may be helpful in preventing colon polyps. For more on this subject please see our article on Aspirin as a Preventative Therapy against Cardiovascular Events. Pre-cancerous tissues produce COX enzymes, which lead some researchers to conclude that blocking the enzyme could stop or even prevent the growth of cancerous cells.
Patients in the other trials now ongoing by the NCI will be informed of the results of the study, as will the safety committees for these studies. Dr. David Graham, the FDA drug safety official who testified recently about the inadequacies in the agency in regards to drugs that are already on the market commented that this is just one more example to show how weak the drug safety system actually is.
Many of us feel that instead of having the drug industry finance the approval process for a drug at the FDA, it should be the responsibility of Congress to see that the agency is fully funded and not depend on the industry for its financing.
(12/15/04)-The FDA has approved a new drug label for Pfizer Inc.'s arthritic pain medication Bextra that adds a warning about a risk of heart and blood-clotting problems for patients who recently had coronary artery bypass graft surgery. The warning also included a caution by users who are allergic to sulfa products.
The FDA said on its Web site that it believes the benefits of the drug outweigh the risks when used on the right patients. An advisory panel is due to report back to the FDA as to the safety of all COX-2 products in February 2005. The new label also strengthens a warning about the possibility for serious skin reactions, including two types that can result in death.
(12/2/04)- Novartis said that it was temporarily withdrawing it application to have its COX-2 inhibitor Prexige, approved in Europe, pending an overall review by the European Medicines Agency of the safety of all COX-2 inhibitors. In the U.S., the FDA expects to have the report from the panel that will be analyzing the safety of COX-2 inhibitors available in February 2005.
An analysis of the latest prescription drug statistics available from IMS Health, a pharmaceutical consulting firm, and Impact RX, a firm that tracks the daily prescribing practices of a nationwide sample of physicians reveals some interesting data. The upsurge in sales of Celebrex and Bextra that followed immediately after the withdrawal of Vioxx from the market at the end of September is now tapering off sharply.
It seems as if the doctors are turning to the older anti-inflammatory drugs like ibuprofen and naproxen as medications for their patients who were on the COX-2 inhibitors. One brand name drug that also seems to be benefiting from the withdrawal of Vioxx is Mobic, a drug made by Boehringer Ingelheim of Germany. Mobic is considered to be in the same general class as ibuprofen and naproxen, but unlike these two generic drugs, Boehringer is actively promoting it, since you must have a prescription in order to be able to buy it.
Total sales of COX-2 inhibitors dropped from 3.84 million in October from 4.48 million in September, which was the last month that Vioxx could be prescribed for usage. According to IMS Health sales for Mobic surged to $61.5 million in October from $43.5 million in September.
Sales for Bextra accounted for 11% of the new prescriptions written by primary care physicians by late September. Impact RX now shows that Bextra accounts for only 2% of these new prescriptions. Celebrex accounted for 14% of the new prescriptions in late September, but again according to Impact RX this number has dropped to 11%.
(12/1/04)- Since Vioxx has been removed from the market and all COX-2 inhibitors have come under a cloud in regards to their safety, it is important that we look at some of the alternative treatments that are available to individuals who suffer from the pain of rheumatoid arthritis. Harold Rubin has been taking glucosamine for his joints for several years now. He believes that it has been helpful to him.
We received an e-mail from David D. Dowse, Director of The Arthritis and Glucosamine Information Center, and we do think it could be helpful to you to visit their site. The site contains a wealth of information, and is especially meaningful at this time. The site is located at: www.glucosamine-arthritis.org .
(11/27/04)- Evidence of a study that was commissioned and paid for by Merck to UnitedHealth Group, nearly a year before the company voluntarily withdrew the drug Vioxx, indicated that the drug posed a cardiovascular risk. The study was an analysis of patient records from the UnitedHealth Group. The study compared the relative rates of heart attack and stroke in people taking, Vioxx; Celebrex and traditional over-the-counter pain medications. The results indicated that Vioxx posed an increased risk of heart problems, compared with the other drugs used in the study. Dr. Alexander Walker, an executive at the Ingenix unit of UnitedHealth led the study group.
Dr. David Graham, director for science and medicine in the FDA's safety office, told the Senate Finance Committee on November 18th that his agency discounts recommendations from its own safety researchers. He also testified that his agency does not deal appropriately with safety concerns once drugs have been approved and are on the market. Sandra Kweder, deputy director of the FDA's office of new drugs said at that same hearing that the drug review divisions of the FDA "work extremely closely with our colleagues in drug safety".
Dr. Graham, the FDA employee who testified before the Senator Chuck Grassley's Senate Finance Committee that the agency's safety office had pointed out the increased risk associated with Vioxx, has stated that he has received several threats against him and his family because he is a "whistle blower".
(11//04)-Dr. Lester M. Crawford, acting commissioner of the FDA backed away from the statement that Curt D. Furberg has been removed from the advisory panel that will report back in February as to the safety of Vioxx. Originally it was announced that Curt D. Furberg, a professor at Wake Forest University, Winston-Salem, N.C. would be removed from the FDA panel that will be reporting to the agency in February as to the safety of the COX-2 inhibitors, the class of drugs that includes Vioxx, Celebrex and Bextra. Dr. Furberg may be removed from the panel because of comments he made that appeared in the New York Times in which he said that Bextra appeared to be very similar to Vioxx in its chemical composition.
"They said that because I had taken a public position, I was disinvited," Dr. Furberg said. He will be able to speak before the panel as part of the public-comment hearing period. Dr. Furberg was quoted in the Times article as saying that an analysis that he had helped to do had found that patients taking Bextra might be at a higher risk for heart attack or stroke. He will, however still be permitted to stay on the FDA's drug safety and risk management advisory committee.
(11/12/04)-William B. White, professor of medicine at the University of Connecticut is the author of a study that found that there wasn't any excess cardiovascular risk for patients taking Bextra for arthritic pain. The results of his study were published this year in the American Journal of Therapeutics. Dr. White feels that it was erroneous to merge data from two different types of patients, namely arthritis and heart-surgery patients.
Dr. Fitzgerald's analysis was based on a total of 7,771 patients of whom 5,930 were given Bextra and 1,841 were given a placebo. There were a total of 45 heart attacks and strokes among patients who took the Bextra, and 7 in the placebo group. When heart attacks alone was counted, there were 16 among the Bextra patients and 2 among the placebo group. The patients in both groups consisted of both heart surgery patients and those who were getting the drug only for their arthritic pain.
Pfizer has argued that although the risk is higher for those patients who had heart surgery, the same was not true for those patients who were taking the drug for the arthritic pain. In addition, many of the heart surgery patients got the intravenous form of Bextra, and not the pill form of the drug. Dr. White also argues that the doses given to the heart surgery patients were much higher than those given the drug for routine care.
Next week both the House and the Senate will have committee hearings on the COX-2 issue, and also quiz the FDA as to their action, or lack of action in the matter. An FDA advisory panel is also scheduled to release the results of its review of the whole situation sometime in February.
(11/11/04)-According to a study, which pooled data from 5,930 patients taking part in 12 trials, found 2.19 times the number of heart attacks or strokes among patients given Pfizer's pain killer Bextra, compared with those given a placebo. The preliminary results of the study were presented on November 9th at the American Heart Association meeting in New Orleans.
Dr. Garret A. FitzGerald, a cardiologist and pharmacologist at the University of Pennsylvania, who headed the study group, said in an interview that was given after the presentation that: "This is a time bomb waiting to go off." Dr. FitGerald is considered to be one of the world's leading experts on COX-2 drugs, a class of medicine that includes Merck's Vioxx which has recently been removed from the market and Pfizer's Celebrex and Bextra. Bextra is considered to be Pfizer's next generation painkiller drug to Celebrex and it garnered over $687 million in sales last year.
Pfizer had previously announced that it would add a "black box" warning to Bextra's label that would note that the drug could cause fatal skin rashes. Pfizer also acknowledged that it had known about the high risk to heart surgery patients who used Bextra two months before it made the official announcement. The company had previously stated that it had no evidence that either Celebrex or Bextra caused the same increased risk of heart attack or strokes as did Vioxx.
Dr. FitzGerald also provided the results of his investigation into the mechanism as to why COX-2 medicines may lead to heart troubles. Using mice, Dr. FitzGerald said, that in inhibiting the COX-2 enzyme, this might reduce the heart protection of estrogen.
(11/8/04)- Researchers of a study, the results of which were published in the British medical journal The Lancet, concluded that Merck and federal officials should have pulled its painkiller drug Vioxx much sooner than they actually did. The study pooled data from 25,373 patients who participated in 18 clinical trials conducted before 2001. They found that patients taking Vioxx had 2.3 times the risk of heart attacks as those given placebos or other pain medications.
The editor of Lancelot, Richard Horton wrote in an editorial that accompanied the study that both Merck and the FDA "acted out of ruthless, shortsighted and irresponsible self-interest". Committees in both the House and Senate are now investigating the whole situation with Vioxx and the FDA in regards to the safety issue.
The issue in the case of Merck and Vioxx revolves around when the company became aware as to the increased risk for heart attacks and strokes faced by patients taking the drug. The increased risk of blood clots forming in those taking the drug, especially among those who were at high risk for heart attacks, is another key question in looking at this matter.
A Merck memo dated November 21, 1996 states that in a trial of the drug "there is a substantial chance that significantly higher rates" of cardiovascular problems would be seen in the Vioxx group. A similar view was expressed in a February 25, 1997 e-mail by a Merck official, Briggs Morrison.
We do not wish to take paragraphs from this article out of context, but here
is but one of the paragraphs that you will come across in this article which
dealt with this subject and was written in the latter part of 2001:
" Many researchers are becoming more aware of the possible side effects that occur when COX-2 inhibitors are used by patients suffering from rheumatoid arthritis. COX-2 inhibitors caused fewer stomach ulcers than many other pain relievers, but as they have had a higher, though relatively low, risk of heart attacks than patients taking the older pain relievers. Several doctors said that they are worried about the possibility of heart attacks because many of the arthritis patients taking the drugs are elderly, and have a higher risk of cardiovascular problems to begin with. Thus we come back to the same question as to whether or not aspirin should be used in connection with COX-2 inhibitors?"
We also include herein the paragraphs that we wrote back in the latter part
of 2000 regarding the Vioxx Gastrointestinal Outcomes Research (VIGOR) study:
" Merck originally announced the preliminary results of its gastrointestinal (GI) trial of Vioxx done under the study name of VIGOR in a letter to investigators in late March 2000. The results of the study were publicly released May 24, 2000. The trial was based on comparisons on 8,076 patients with rheumatoid arthritis who were administered 50 mg of Vioxx once daily, or 500 mg of the generic naproxen twice daily.
The trial began in January 1999 and ended earlier than expected. Merck submitted the data to the FDA hoping to gain removal of the current NSAID GI warning. Vioxx showed a statistically significant reduction in perforations, ulcerations, obstructions and bleeds vs. naproxen. Vioxx users had 54% fewer painful ulcers, stomach holes and gut bleeding than those taking naproxen.
The rate of bad side effects was 4.5% per year in the naproxen patients, compared with 2.1% among the Vioxx users. Vioxx reduced the most severe side effects, including stomach blockages and severe bleeding by 57%. Unexpectedly, Vioxx had a higher rate of cardiovascular side effects (such as thromboembolic events) than naproxen. Because of these results, Merck will allow patients to use low-dose aspirin in future clinical trials for Vioxx as well as when their new generation COX-2 inhibitor, MK-663 is used. The aspirin is used to help prevent formation of blood clots that can cause heart attacks and strokes."
(11/2/04)- The front page of the November 1, 2004 edition of the Wall St. Journal has an article written by Anna Wilde Mathews and Barbara Marinez entitled "Warning Signs-E-Mails Suggest Merck Knew Vioxx's Dangers at Early Stage". The main thrust of the article is that Merck officials first became aware of the negative side effects of Vioxx as early as November 21, 1996. The Journal was given certain e-mails and other corporate documents that indicated that the drug could increase the risk of heart attack or stroke for those who took the drug over a long period of time..
To quote from the article: "But internal Merck e-mails and marketing materials as well as interviews with outside scientists show that the company fought forcefully for years to keep safety concerns from destroying the drug's commercial prospects." The article goes on to state: "On March 9,2000, the company's powerful research chief, Edward Scolnick, e-mailed colleagues that the cardiovascular events 'are clearly there' and called it a 'shame".
Ted Mayer, an attorney representing Merck, said that the e-mails and marketing materials were "taken out of context" and that the company would answer the allegations at a later date. We at therubin certainly do not claim to be medical experts but as we wrote this article over the last few years it seemed apparent to us that the studies that we wrote about were showing that there was a great deal of concern in this area. It will now be up to the court system to judge what the facts of this matter prove to be.
On another front the FDA issued an approval letter for Merck's next generation pain reliever drug Arcoxia, but the agency will require more safety and efficacy data before it can approve the drug for usage by the public. Arcoxia is Merck's next generation COX-2 drug that was meant to take the place of Vioxx for the treatment of pain. In effect this means that it will be at least 2 years before Arcoxia is eventually approved for usage by the public.
(10/27/04)-The European Medicines Agency announced a wide ranging safety review of many of the COX-2 inhibitors in order to study their effects on cardiovascular health. The agency is based in London and relies to a large extent on a network of 3,000 scientists and health experts. The U.S. FDA also has announced that it too will be conducting a wide-ranging study as to the effect of the COX-2 inhibitors on the cardiovascular system.
The European review is expected to take between 5 to 6 months before it is completed. The agency termed the study as a "precautionary measure". After the review is completed the agency will issue a report to the European Commission, the administrative arm of the European Union. The unit conducting the review studied the safety of COX-2 inhibitors in 2003, and did not recommend any changes to be made in connection with the safety of heart patients.
Celebrex, the Pfizer COX-2 inhibitor is sold under the name of Celecoxib in Europe. Novartis' pain-killing medication has been approved for sale in England under the name of Prexige. It is estimated that about 27 million patients in the U.S. used Celebrex so far in 2004. Pfizer has estimated that about 7 million patients have taken Bextra since its introduction in late 2001.
Pfizer has also announced that it plans to fund a large-scale clinical trial of Celebrex's ability to prevent heart attacks and strokes in patients with serious cardiovascular disease. Some heart specialists feel that inflammation in the body leads to heart attacks and strokes and that Bextra can prevent this inflammation from taking place. The company expects to try to enlist patients in the study in the next few months. The study is expected to track the patients for 2 years. To participate in the study the patients recently must have survived acute coronary syndrome, a condition stemming from the narrowing of the arteries that supply oxygen to the heart.
(10/21/04)-Pfizer Inc. announced that there did appear to be increased risk of stroke and heart attack for high-risk patients taking its pain killer drug Bextra. These high-risk patients include those who, like former President Bill Clinton, who have undergone coronary bypass operations. As it relates to this type of patient, Bextra has only been studied for one year. Please keep in mind that the Vioxx problem for increased risk for stroke and heart problems did not occur until after the elapse of 18 months.
Bextra is Pfizer's next generation of pain killing drug to Celebrex. In the general surgical studies that have been performed so far Bextra has been used in combination with an injectible form of a drug called Dynastat. Dynastat has not been approved for usage in the U.S.
The first study involved 450 patients, 300 of which received Bextra and Dynastat. All the patients had the option of giving themselves morphine and opiates, and everyone received low-dose aspirin. This study showed a slightly higher risk for adverse events, but it was not statistically meaningful.
The second study involved 3 groups of 500 patients, each of which had undergone coronary bypass surgery. Group 1 received a placebo meant to look like Dynastat and a sugar pill that looked like Bextra and a standard narcotic drug. Group 2 received an injectible placebo, Bextra and the standard pain drugs. Group 3 received Bextra, Dynastat and other drugs.
In the case of Group 1, 3 people suffered severe coronary events. In the case of Group 2, 6 people in the Bextra group experienced severe coronary events, and in the case of Group 3 (the Bextra-Dynastat group) 11 people suffered severe coronary events.
Since 2002, the Bextra product label has included the information regarding the risk of a very rare but serious skin reaction.
10/11/04) Experts who attended a conference sponsored by the federally funded Centers for Education and Research on Therapeutics in 2003 wrote that the "current U.S. system for assessing the risks of therapeutics is outdated and inadequate." The current Vioxx controversy has thrown even more light on how inadequate and dangerous is the system for checking into approved medications in this country.
Once a drug has been approved for sale by the FDA, the agency has only limited authority to order that a safety study be conducted for the drug. It can however require that the company change the drug's labeling statement to reflect the increased risks that users of the drug may be subjecting themselves to. The FDA oversees a database that gets reports on adverse drug reactions, which showed almost 280,000 such incidents last year. For our article on this matter please go to Adverse Drug Effects
Pfizer Inc. has released a statement stating that it is presently running three trials involving a total of 6,000 patients that have been under way for several years in connection with its pain killer drug Celebrex. Two of the tests are assessing whether Celebrex may be useful in preventing colorectal cancer in patients who have had pre-cancerous growths removed from their colons. Please note that there is some clinical evidence to show that aspirin may be useful in preventing colon cancer. For our article on this topic please go to Aspirin as a Preventive Against Cardiovascular Events. The company expects these two studies to continue for another four years. The National Cancer Institute is funding one study, while Pfizer is funding the second study.
The third study, which is sponsored by the National Institute of Health, is examining Celebrex's potential to prevent or slow the progression of Alzheimer's disease. In this study Celebrex is being compared to a placebo.
Bayer AG's Aleve (a brand name for naproxen) is part of a trial to also test to see if it can prevent or slow the progression of Alzheimer's disease. In the Aleve study, it is being compared to the results of a placebo, and it is part of a trial known as the Alzheimer's Disease Anti-Inflammatory Trial (ADAPT). This study is sponsored by the National Institute on Aging, and has enrolled more than 2,400 patients over the past three years.
As part of the approval process, the FDA can require that so-called phase four studies be done later, after the drug goes on the market. According to an FDA report in March 2003, there were 1,338 such post-marketing commitments for drugs as of September 30, 2003. According to the report 65% of the studies had not been initiated yet.
(10/4/04) Merck & Co. has announced a complete withdrawal and recall of its pain-killing drug Vioxx. The decision to withdraw Vioxx from the market was based on the results of a trial Merck was conducting to assess the drug's ability to prevent a recurrence of polyps that were a precursor of colon cancer.
The 3-year clinical trial involved 2,600 patients, half of who took a 25-mg dose of the drug, and half of who took a placebo. Among the patients taking Vioxx for more than 18 months, there were 15 heart attacks or strokes for every 1,000 patients compared with 7.5 per thousand who were on the placebo. For patients who took the drug for 18 months or less, there was not any increase in cardiovascular risk.
Please keep in mind that the European Agency for the Evaluation of Medicinal Products considers the whole COX-2 class of drugs to have increased cardiac risk. Also please keep in mind that Celebrex, Pfizer's pain killing drug has been shown to be not as effective as Vioxx in reducing the adverse side effect of stomach bleeding. Several studies have also shown that there is a potential for kidney and liver damage involved for those taking COX-2 drugs.
It is estimated that Vioxx is a drug that is being taken by about 2 million people worldwide at the time of this withdrawal of the drug. The cheaper non-steroidal anti-inflammatory drugs (NSAIDs) that are available include aspirin, ibuprofen and naproxen, all of which are available over the counter. These drugs which include such names as Advil, Aleve and Motrin usually have to be taken more than once a day and do increase the risk of gastrointestinal bleeding.
Merck said those patients in the U.S. wanting a refund for unused Vioxx may return the unused drug in it original pharmacy packaging by regular mail to NNC Group, Merck Returns, 2670 Executive Drive, Indianapolis, IN 46241. Include your name, address and phone number, and the receipt from the pharmacy in the mailing. Merck said that customers with questions should call their toll free number at 888 368 4699 or on the Web at www.vioxx.com
As you now look back on the articles that we have written on this topic you can gain a good historical perspective on this whole question. Remember that we at therubins constantly update our articles, but history oftentimes shows some interesting previous developments in this whole area. In a positive vein, Johnson & Johnson won expanded approval from the FDA to market Remicade, which it began selling in 1998, for patients who newly diagnosed with rheumatoid arthritis of the joints. The drug had been previously approved only for patients who were not helped by methotrexate, an older treatment for the disease.
The results of an independent study that was funded by the Canadian Institute of Health Research, a government agency, showed that Merck & Co.'s Cox-2 inhibitor Vioxx carries a higher risk for heart problems than alternatives. The lead researcher for the study was Mohammad Mamdani, a clinical pharmacist at the Institute for Clinical Evaluative Sciences in Toronto. No drug company funding was used.
The records for about 1.3 million elderly patients who were 66 years and older were studied. The prescription records for 15,000 patients taking Vioxx, 19,000 patients taking Celebrex and 5,000 patients taking older non-steroidal anti-inflammatory drugs were studied. About 100,000 randomly selected patients not taking these pain drugs served as the comparison group.
Researchers found that elderly people taking Vioxx had an 80% increase in hospital admissions for congestive heart failure within one year of starting therapy compared with patients not taking NSAIDS. Patients taking Pfizer's Celebrex had the same rate of hospitalizations for congestive heart failure as people who weren't using any NSAIDS at all. Patients taking the older NSAIDS, such as ibuprofen, had a 40% increase in such hospitalizations compared with those not taking any of the drugs.
The absolute risk for hospital admission for any patient taking Vioxx is low, since it was only less than 1% of the patients taking the drug. Vioxx and Celebrex are part of a subcategory of NSAIDS called Cox-2 inhibitors.
The U.S. Court of Appeals for the Federal Circuit in Washington upheld the dismissal of the $3 billion lawsuit brought by the University of Rochester against Pfizer Inc. for patent violation in connection with the pain-killing drug Celebrex. The appeals court upheld the decision of the trial judge, who ruled that the patent held by the university was invalid.
The University of Rochester had filed a patent infringement suit against Pfizer (/Searle/Pharmacia) the manufacturer and co-marketers of Celebrex. At the time of the institution of the suit officials of the university stated that the purpose of their suit was to negotiate royalties rather than have the drug removed from the market.
The patent was based on the work on Cox-2 inhibitors done by Dr. Donald Young, a professor of biochemistry and medicine, assisted by Michael K. O'Banion and Virginia D. Winn. Nonsteroidal anti-inflammatory drugs, aspirin, and ibuprofen work by blocking both the Cox-1 and Cox-2 enzyme. They also have a negative side effect since usage can lead to ulcers and gastrointestinal bleeding.
The appeals court, which specializes in U.S. patent law said the patent was invalid because the university did not adequately describe what it said it had invented. Gerald Dodson, the attorney for the university had no immediate comment on the matter.
The cyclo-oxygenase (COX) enzyme is involved in pain and inflammation. The COX-1 enzyme is involved in protecting the lining of the stomach from acids. The patent application was filed in 1992. Scientists from 2 other universities came up with the same discoveries at just about the same time. This was done at the University of California, under Dr. Harvey R. Herschman, and at Brigham Young University under Professor Daniel L Simmons. The lawyers for the university said they had not started any negotiations with Merck the manufacturer of Vioxx, since they wanted to concentrate their action against Celebrex.
Merck & Co. has submitted it new rheumatoid arthritis drug Arcoxia to the FDA for approval to market the drug in the U.S. Arcoxia, which is already being sold in 36 countries in Europe, Latin America and Asia, is Merck's next generation drug to Vioxx. Merck said that it would be seeking approval for Arcoxia to treat several forms of arthritis. Because of the latest data which shows the increased risk of heart attack or stroke from usage of Vioxx for more than 18 months there is expected to be a lengthy delay in FDA approval for Arcoxia, a drug which is very similar to Vioxx.
A study from Harvard University-affiliated Brigham & Woman's Hospital in Boston that was funded by Merck & Co. found that Vioxx, which is manufactured by Merck increases the risk of heart attack for patients who use the drug in connection with the pain from rheumatoid arthritis. Daniel H. Solomon who headed the study, which looked at the records of 54,475 Medicare patients, all of them over 65 years of age.
The risk for having a heart attack was greater for those taking Vioxx than it was for those taking the competing drug Celebrex which is made by Pfizer & Co., and also for those patients who were not on any painkillers at all. Researchers found that the greatest risk occurred in the first 90 days in which a patient was taking Vioxx. Even though the actual risk is not that great, when you realize that many millions of people are taking these drugs you realize that the issue can be of great consequence to all of us. These conclusions are similar to those reached by researchers at Vanderbilt University last year when they examined the records of 24,131 patients taking Vioxx.
A study done by researchers in Hong Kong showed that arthritis sufferers who have had ulcers should not take either Pharmacia/Pfizer's arthritis drug Celebrex, nor AstraZeneca's ulcer medication Prilosec which was given in combination with the generic anti inflammatory drug clofenac.
The study also showed that neither treatment protected as many patients from dangerous kidney complications as past studies had indicated. The study included 287 patients who had a previous bleeding ulcer and so were at high risk of developing another, potentially life-threatening ulcer. It had been hoped that the Cox-2 inhibiting drugs, which do not block the action of the Cox-1 enzyme would therefore not affect the stomach lining. According to Dr. David Y. Graham of the Veterans Affairs Medical Center in Houston: "The results were unexpected. Neither regimen provided a good or even acceptable level of protection from recurrent bleeding."
About 25% of those in the Celebrex group and 31% in the diclofenac/Prilosec group suffered kidney complications, including high blood pressure and swollen ankles; about 6% in each group suffered life-threatening kidney failure.
Novartis released data at the European Union Against Rheumatoid Arthritis which supported the efficacy of Prexige, their new COX-2 inhibitor drug which could compete with Pfizer's Bextra and Celebrex, and Merck's Vioxx. There has been some concern expressed however about the cardiovascular profile of the drug. The most important trial for this drug called TARGET has not yet been completed. Interim results for this trial are due to be completed by the end of the year but Novartis has indicated it does not plan to release the interim results. Final results for the trial are due to be completed by the end of this year.
The FDA has issued a warning in connection with people who develop a rash after having taken Bextra, the next generation of pain killer after Celebrex, manufactured by Pfizer & Co (Pharmacia). If you develop a rash after having taken Bextra, you should stop taking it immediately because it has been linked to some rare but life-threatening skin disease. The FDA has received about 20 reports of serious reactions, including the skin diseases Stevens-Johnson syndrome, toxic epidermal necrolysis and exfoliative dermatitis as well as allergic reactions among Bextra users since sales began in March. The condition can be life threatening and has already resulted in the hospitalization of some other users of the drug. Pfizer/Pharmacia has written thousands of doctors alerting them to the problem.
An advisory panel of the FDA concluded its hearings in regards to the labels on common painkillers such as acetaminophens, ibuprofen, naproxen and aspirins. As a result of these hearings the advisory panel will recommend to the FDA that stronger warning labels are needed for these painkillers. The FDA was expected to act on these recommendations early in 2003. The panel did not question the safety of these products when taken as directed, but questions have arisen in connection with misreading of the labels and overuse of these products.
The panel found evidence that thousands of Americans unwittingly take toxic doses of acetaminophen, which is the main ingredient in almost 200 over-the-counter cold and headache remedies, including Tylenol. The panel voted 23-1 in favor of recommending to the FDA that stronger warnings be required on the labels of all acetoaminophens. Acetaminophen is also found in painkillers such as Percocet and Vicodin.
The panel recommended that every package of a drug that contains acetaminophen states in bold type on the label that it contained the ingredient. It also recommended that the label state in bold letters that taking more than the recommended dosage could result in liver damage. Johnson & Johnson has already undertaken this steps in connection with the labels on Tylenol.
The panel also stated that certain groups of patients, such as the elderly should be warned that they risk stomach bleeding or kidney failure by taking the class of medicines known as nonsteroidal anti-inflammatory drugs known as NSAIDs. Included in the NSAID category are aspirin, ibuprofen, found in Motrin and Advil, and naproxen found in Aleve.
Researchers have noted that acetaminophens (Johnson & Johnson's Tylenol is the best known of these products) can cause liver problems over time, and aspirins can cause gastrointestinal bleeding with prolonged use. John Jenkins, head of the FDA's Office of New Drugs stated that "We'd like to do a better job of preventing some of these (adverse effects)." The advisory panel's recommendation is usually upheld by the final decision of the FDA.
In an interesting side-note to the panel's hearing, each product side in the debate is emphasizing the weakness of the other side, while minimizing the weak points of their own drug. An FDA review of acetaminophen overdoses found that consumer calls to poison-control centers about acetaminophens decreased from 111,175 in 1995 to 108,102 in 1999. Deaths however associated with the drug's overdose rose from 76 to 141 in the same period. The number of deaths included death from suicide as well as from accidental overuse.
Many financial experts the main reason why Pfizer Inc. took over Pharmacia Inc. was so that it could gain full control over the sales of Celebrex the blockbuster anti-arthritic drugs that both companies were originally co-marketing.
At the time of the merger Henry McKinnell, Pfizer's chairman and chief executive officer stated that the company would press more aggressively what he believed was Celebrex's major advantage over Merck & Co's. Vioxx… that it hasn't been linked to any heart problems.
Vioxx on the other hand claims that it has not had the stomach problems that have been associated with those who have been taking Celebrex. Many experts feel that most patients would fare just as well with the cheaper generic pills-including aspirin and ibuprofen-known as NSAIDs. A daily dose of Celebrex costs about $2.39 while a daily dose of Vioxx costs about $2.44. One of the common NSAIDs called diclofenac sells for about $.64 a daily dose and generic naproxen sells for about $.30 cents a daily dose. ( Sources: Drugstorecom; WSJ research)
The two most popular nutritional supplements that some research indicates eases the pain of osteoarthritis are glucosamine and chondroitin sulfate. Although Vioxx may increase the risk of heart attacks and Celebrex's label warns that it may cause stomach ulcers, nutritional supplements are thought to be free of such side effects.
If you do choose to use these nutritional supplements please keep in mind that the FDA does not regulate the production of supplements the way it regulates the production of drugs. Also choose a reputable brand and look for the letters "USP", which indicates that the manufacturer has followed the guidelines of the US Pharmacopia, a not-for-profit group that sets quality standards for medicines. The recommended dosages are 1,500 milligrams a day for glucosamine and 1,200 milligrams a day for chondroitin sulfate. Please be aware that chondroitin can cause bleeding in people who take blood thinners.
Merck will conduct a 6,000 patient study versus diclofenac on osteoarthritis patients for both gastrointestinal and cardiovascular safety data. Arcoxia is only one of several new entrants in the COX-2 battle. Pfizer/Pharmacia's has their new product Bextra already on the market as the successor to its original entrant of Celebrex. AstraZeneca is chomping at the bit with Crestor as its entrant in the COX-2 derby. Novartis's COX-2 entrant, which is awaiting FDA approval, is Prexige, and Abbott Labs' entry in the field for the treatment of rheumatoid arthritis is D2E7.
The FDA ruled that Celebrex must continue to carry a warning on its label that it can cause serious ulcer complications. It also did rule that the revised label could include the fact that the drug did not increase the risk of heart attack or gastrointestinal (GI) attack any more so than generic pain relievers such as ibuprofen or diclofenac.
Neither Celebrex nor Vioxx, the anti-arthritic drug made by Merck, has been shown to reduce pain better than ibuprofen or other low-cost pain relievers. The FDA requires Merck to carry the warning on the Vioxx label about the potential risk of heart attack, but the agency did state that Vioxx did significantly lower the risk of ulcers more so than did naproxen, an older pain reliever.
There is an editorial written by Dr. Pere Juni, a senior researcher at the University of Berne, in Switzerland, and two other doctors, that appeared in the June 1,2003 issue of The British Medical Journal. They harshly criticized one of the main studies used by Pharmacia to promote its best selling arthritis drug Celebrex.
The study in question concluded that Celebrex was safer than other widely used arthritis drugs, because it caused fewer ulcers had "serious irregularities". A spokesman for Pharmacia, Dr. Steve Geis, a vice-president for clinical research said that the company stands by the previously announced conclusions.
The study in question was reported on in 2000 in the Journal of the American Medical Association. The study concluded that patients taking Celebrex suffered fewer serious ulcer complications that those taking ibuprofen or diclofenac. The Washington Post later published an article stating that the published data only covered the first 6 months of the test rather than the full year data for which time period the study lasted for. According to Dr. Juni and his colleagues, much of the safety data that appeared for the first 6 months of the trial disappeared when considered on the full year basis.
Pharmacia and the doctors it hired for the study said they omitted the last 6 months of data because many patients dropped out in the latter half of the study, skewing the results. The high-drop out rate left more high-risk ulcer patients in the Celebrex test group than there were in the other groups. Dr.Juni and his colleagues feel that Pharmacia has a responsibility to the medical and scientific community to point out all the details of the study, not only that part which is most favorable to the drug.
One of the most difficult problems to evaluate whenever a new drug is introduced deals with the effect the drug may have on other areas of the patient's health. A drug may be very good for one purpose and yet it may cause some serious problems in other areas. In our article below we originally examined some of the results of the new COX-2 inhibitors in the battle against arthritis pain. Recently however there are more and more indications that some of the drugs that have been effective in treating Rheumatoid Arthritis may also be effective in the fight against colon cancer.
Ron Winslow wrote an article in the May 22 edition of the Wall Street Journal entitled " Arthritis Drug Celebrex Shows Promise as Cancer Weapon". The article reported on the results of a small study whose results were announced at the recently concluded meeting of the American Society of Clinical Oncology. More studies continue to show that COX-2 is present in high quantities in a wide range of tumors.
According to Andrew Dannenberg, director of cancer prevention at New York Presbyterian Hopitals's Cornell campus, an overabundance of COX-2 can interfere with the normal life cycle of cells by preventing their natural death, thus resulting in the uncontrolled growth of cancer cells. COX-2 may also promote growth of blood vessels that feed tumors, and may also regulate the process associated with metastasis. No one is claiming that COX-2 inhibitors prevent cancer, it is possible that in combination with other drugs, they may be used to prevent the growth of cancerous cells.
The December, 1999 edition of Nature Study looked at the results of a study done by some researchers at the Veterans Affairs Medical Center in Long Beach, Calif. The study was done on rats who had been administered the older arthritis drug indomethacin and the newer COX-2 inhibitor drugs. It concluded that both slowed the development of new blood vessels in rat cells. By slowing the growth of new blood vessels you can therefore slow the growth of cancerous tumors.
One of the negatives that this study showed was that the latest generation of arthritis pain drugs would also slow the ulcer healing process. An article in the New York Times by Gina Kolata on January 18th, 2000 stated that the National Health Institute would oversee tests to see if the COX-2 inhibitors can prevent colon cancer as well as treat Rheumatoid Arthritis. It was determined that the older drugs slowed the development of new blood vessels in rat cells to a greater extent than did the COX-2 inhibitors. We caution you by pointing out that these tests were not performed on humans.
In 1991 the New England Journal of Medicine published the results of a landmark study begun in 1983. The conclusion of that study was that people who took 16 or more aspirins a month for at least a year had about 1/2 the risk of death from colon cancer as people who didn't regularly use aspirin. A study involving 104,217 people in the Tennessee Medicaid program also showed that there were far fewer cases of colon cancer in elderly people who used aspirin regularly to treat their arthritis than amongst those who did not use aspirin regularly.
Please keep in mind that since aspirin and the NSAIDS such as Advil and Aleve are all off patent there is no financial inducement for the drug companies to investigate the possibilities of their anti-cancer properties.
Many of us, including this writer, have taken baby aspirins for many years as a heart failure preventive. This interesting finding may now also come into play in the fight against rheumatoid arthritis and colon cancer. Scientists at both Merck & Co. and also at the Searle division of Monsanto Co. believe that their new anti-arthritic drugs may also be useful in the fight against colon cancer.
Colon cancer killed about 48,000 people last year, which was second only to lung cancer. The F.D.A has now approved Celebrex, a non-steroidal drug to be marketed for treatment of certain polyps, which greatly increases the risk of developing colon and rectal cancer at an early age. The mechanism of action was related to the drug acting as an anti-inflammatory agent. Now the FDA has approved its use for the treatment of a rare genetic disorder that causes intestinal polyps.
The condition is called familial adenomatous polyposis (FAP). It increases the risk factor for developing colon and rectal cancer. The FDA made it clear that this medication should only be used in addition to current treatments, which usually involve removal of the lower intestine. The study cited for approving Celebrex for use in FAP involved 83 patients and showed that those patients using Celebrex developed 28 percent fewer polyps than those who used a placebo did. In this study, the main side effects of Celebrex were indigestion and diarrhea. The FDA is also requiring Searle to undertake more studies to determine whether reducing polyps was in fact beneficial to patients. Consult your physician for further information on this medication.
Both aspirin and these 2 drugs block the action of the natural enzyme referred to as COX-2 that is involved in some manner with inflammations. Many researchers feel that COX-2 enzyme affects the cell growth occurring excessively in cancer. If both aspirin and these 2 drugs can turn off the switch that produces the excess cell growth in colon cancer it may do the same for other cancers. Both these companies and Bayer are presently engaged in extensive testing to see if this preventive action will affect colon cancer. Both Merck and Searle are also presently testing COX-2 inhibitors to see the affect it may have on Alzheimer's disease.
The FDA did grant Merck approval to add to the label of Vioxx the fact that the drug seems to protect the user against gastrointestinal bleeding. The label must however add as a precaution that it may increase the risk of heat attack. Vioxx has won approval to include on its label that it treats rheumatoid arthritis, osteoarthritis, acute pain and menstrual pain.
It is estimated that there are about 100,000 hospitalizations, and 16,500 deaths each year due to some extent to the usage of standard pain pills such aspirin and ibuprofen in connection with ulcers.
Some analysts suggested that the Arcoxia application was withdrawn because of concern over the drug's potential cardiovascular risks. A spokesman for Merck did not indicate a timetable for resubmission of the application. The advisory panel for the FDA will be meeting some time in May to review the safety of the Cox-2 inhibitors. Sales of Vioxx were $2.1 billion in 2001 making it the 6th best-selling drug, compared to Celebrex, which had $2.4 billion in sales in 2001 making it the 3rd best-selling drug.
Pharmacia Inc. and Pfizer have begun co-marketing Bextra, which is their next generation drug to Celebrex. The FDA has approved the drug for treating the signs and symptoms of osteoarthritis and adult rheumatoid arthritis and primary dysmenorrhera (painful menstrual cramping). It has not been approved for acute pain as of this date.
Another question has now come to the forefront to cast another shadow of doubt about Merck's anti-arthritic drug Vioxx. The problem boils down to a question as to whether or not prolonged use of Vioxx causes damage to the user's liver.
A kidney disease known at segmental sclerosis has affected two well-known basketball players, Alonzo Mourning of the Miami Heat and Sean Elliot of the San Antonio Spurs. In the case of Mourning, he had to sit out one-year because of the problem and Elliot had to undergo a kidney transplant operation and is no longer playing pro ball.
Many pro athletes take nonsteroidal anti-inflammatory drugs like ibuprofen and aspirin as well as the prescription drugs Vioxx and Indocin to help overcome arthritic or other painful conditions that may prevent them from playing that day. It is common knowledge that most professional basketball and football players use these drugs. Mourning believes that his long-term use of the drugs over his 12-year career contributed to his disease.
Dr. Gerald Chodak, a clinical professor of urology at the University of Chicago stated as follows: " Decreased kidney function is a known side effect with almost every anti-inflammatory you can think of."
Merck revealed at an drug analysts meeting that the company was disappointed with the recent sales trend of its anti-arthritic drug Vioxx. While sales this year for the drug should total about $2.5 billion, its growth rate has slowed perceptibly lately. The sales rate slowdown has been effected by the August article in the Journal of the American Medical Association that questioned whether the drug increases the risk of heart attacks. The other reason for the sales rate slowdown has been the fact that large managed-care groups are not allowing its members easy access to the drug. The HMO executives do not feel that the drug relieves arthritic pain any better than some less expensive anti-arthritic drugs.
Pharmacia Corp. and Pfizer Inc. announced that the FDA had approved Bextra (R) (valdecoxib tablets), a COX-2 specific inhibitor, for treating the signs and symptoms of osteoarthritis, adult rheumatoid arthritis and the treatment of pain associated with menstrual cramps. In global clinical trials involving more than 5,000 patients, Bextra became the third drug in the class of medicines called COX-2 inhibitors that relieve pain as well as aspirin does, but without causing as many gastrointestinal side effects. It thus joins Pfizer's Celebrex and Merck's Vioxx in the battle against arthritis.
Arthritis affects more than 23 million Americans. Osteoarthritis (OA) is the more prevalent one, affecting 21 million, while rheumatoid arthritis (RA) affects more than 2.1 million. RA is an autoimmune disease that affects joint lining, cartilage and bones. OA is a chronic disorder that causes pain and stiffness, because of the degeneratrion of joint cartilage and adjacent bones.
According to the announcement from Pharmacia "We do not see any evidence of increased risk for any kind of serious cardiovascular problems,". The most common side affects seen in the clinical tests of Bextra were headache, abdominal pain, upset stomach and nausea. The clinical studies had lasted between 3 to 6 months time. The company's announcement further stated that neither Bextra nor Celebrex should be given to patients who suffer from asthma or suffered allergic reactions after taking aspirin or conventional NSAIDS.
The trend for increased drug prices continues unabated as shown by some
recent prices in the update to the Red Book, Merck increased the price of Vioxx
by 9.3%, or 13.5% year over year. The prices of all dosages of Vioxx were
increased. No price increase was seen for Pfizer's Celebrex. The Red Book is a
pharmacist's resource for drug pricing based on "average wholesaler
prices". Once again we ask how accurate is the "average wholesale
price" listing when as, Merck is doing with Vioxx, a drug company
increases the price of a drug whose sales is slowing in the marketplace. Could
it be that the strategy is to increase the price, so it would appear that a
sharper percentage discount is seemingly given when the price is cut? Pfizer
has not changed its pricing for Celebrex whose sales is
holding up better right now than is Vioxx. Pharmacia did announce however that
the FDA has approved the use of Celebrex to include treatment of acute and
menstrual pain in adults.
An analysis of the raw data for the research done by Merck & Co. on Vioxx and by Pharmacia/Pfizer & Co. for Celebrex by Eric J. Topol and Steven E. Nissen, chairman and vice-chairman, respectively, of cardiovascular medicine at the Cleveland Clinic concluded that "Current data would suggest that use of these so called 'COX-2 inhibitors' might lead to increased cardiovascular events." Debabrata Mukherjee, now of the University of Michigan collaborated on the analysis, whose findings were published in the Journal of the American Medical Association.
When the FDA originally approved the drugs, they required both Merck and Pharmacia/Pfizer to include on the label that 2% to 4% of those using the drugs for at least a year could get ulcers. In order to have this labelling changed both companies undertook large studies whose results they presented to the FDA in order to have the warning removed from the labels. This turned into a very embarrassing attempt by Pharmacia because the FDA disclosed that Pharmacia had an additional half-year Celbrex data beyond what it had published.
The 12-month data showed worse results regarding ulcers than did the 6-month data whose results had been published in JAMA. Jay Goldstein, professor of medicine at the University of Illinois at Chicago who was one of the Celebrex's study authors stated that the extra data was not included because a high number of patients dropped out during the study's second six monts. The authors worried that JAMA would not publish the study with such suspect data according to Dr. Goldstein. JAMA's editor, Catherine D. DeAngelis says that Pharmacia and the authors should have told JAMA about the extra data so that the journal would have had all the facts on the matter.
In examining the data presented for the benefit of the FDA in connection with the ulcer matter, the agency became alarmed about the apparently high rate of cardiac events, especially in respect to Vioxx. The agency enlisted Dr. Nissen of the Cleveland Clinic to help evaluate the heart data. Drs. Nissen and Topol determined that according to Dr. Topol, "I wouldn't say this was buried , but the appropriate cautionary flag wasn't raised."
The largest Vioxx study analyzed by the Cleveland Clinic authors included 8,076 rheumatoid-arthritis patients treated for up to 13-months with either Vioxx or naproxen. Forty-five Vioxx patients suffered a serious clot-related event during the study, compared to 20 in the naproxen group. In Pharmacia's yearlong study of 8,059 patients, there was "no significant difference" in cardiac events between patients on Celebrex and those taking other low cost NSAIDs, diclofenac and ibuprofen. The NSAIDs are painkillers that include aspirin, Advil and Aleve.
The Cleveland Clinic researchers compared the rate of cardiac events among Vioxx and Celebrex patients with that in 23,407 medium-risk cardiac patients given a placebo in various heart-attack prevention trials. The annualized heart attack rate in the placebo patients was 0.52%, with Vioxx it was 0.74%, and with Celebrex it was 0.80%.
The study did show that the Vioxx users had half the rate of ulcers and bowel perforations as those taking naproxen. The Celebrex study did not show such positive results re ulcers and bowel perforations. This could be because the Celebrex participants were also taking aspirin. Celebrex failed to prove that it reduced pain quickly, something the Vioxx studies proved. According to Sharon Levine, associate director of the Permanente Medical Group at Kaiser Permanente, " Consumers are paying millions and millions for drugs that, for most of them, appear to have not clinical benefit" over much cheaper pills.
If you look at just the cost factor in comparing Celebrex, Vioxx and ibuprofen or naproxen it is a no-brainer. A one month's supply of ibuprofen or naproxen costs about $20 versus about $77 for Vioxx and $87 for Celebrex. As we all know however cost is not the sole criterion in evaluatingthe total cost-effectiveness of a drug.
In the ongoing battle between Celebrx and Vioxx, a study presented at the American College of Cardiology's meeting in Orlando, showed that elderly hypertensive osteoarthritis patient's taking Merck's Vioxx had an increase in mean systolic blood pressure compared with those taking Pharmacia's Celebrex, who showed no increase in mean systolic blood pressure.
Celebrex was first introduced to the market in 1999 and its introduction was the most successful drug launch in history. Last year the drug had over $2.6 billion in sales. Vioxx was introduced about 5 months later and it was the 2nd most successful drug launch in history. According to the latest figures Vioxx had over $2.2 billion in sales last year.
Both Vioxx and Celebrex cost about $3 a day, versus their generic competitors which cost about 10 cents per day. One of the low-cost generic drugs used to treat rheumatoid arthritis is called methotrexate. If the cost for the generics is less you may then ask why use the COX-2 inhibitors? If however they can be proven to be non-harmful to the stomach and not increase the risk of ulcers the answer would swing largely in their favor.
If one of the drug companies could prove that its drug was less harmful than the other, that would be a big plus in helping it gain a bigger share of this huge market for the drug. Only about 2 % to 4 % of NSAID users develop stomach problems such as ulcers, but there are millions of people who use either the NSAIDs or the COX-2 inhibitors. It is estimated that about 100,000 patients are hospitalized each year as a result of the NSAIDs of whom about 15,000 will die. In the case of the elderly who intake low-dose aspirin to prevent or deal with heart problems the answer to the question becomes quite relevant.
The advisory committee turned down the Pharmacia/Pfizer application to change the warning label but did allow Merck to include the fact on the label that the results were still open re the question of increasing the risk of ulcers.
Merck originally announced the preliminary results of its gastrointestinal (GI) trial of Vioxx done under the study name of VIGOR in a letter to investigators in late March 2000. The results of the study were publicly released May 24, 2000. The trial was based on comparisons on 8,076 patients with rheumatoid arthritis who were administered 50 mg of Vioxx once daily, or 500 mg of the generic naproxen twice daily.
The trial began in January 1999 and ended earlier than expected. Merck submitted the data to the FDA hoping to gain removal of the current NSAID GI warning. Vioxx showed a statistically significant reduction in perforations, ulcerations, obstructions and bleeds vs. naproxen. Vioxx users had 54% fewer painful ulcers, stomach holes and gut bleeding than those taking naproxen.
The rate of bad side effects was 4.5% per year in the naproxen patients, compared with 2.1% among the Vioxx users. Vioxx reduced the most severe side effects, including stomach blockages and severe bleeding by 57%. Unexpectedly, Vioxx had a higher rate of cardiovascular side effects (such as thromboembolic events) than naproxen. Because of these results, Merck will allow patients to use low-dose aspirin in future clinical trials for Vioxx as well as when their new generation COX-2 inhibitor, MK-663 is used. The aspirin is used to help prevent formation of blood clots that can cause heart attacks and strokes.
In the Pharmacia/Pfizer study, called CLASS, 22 % of the patients took aspirin, 78 % did not, along with the drug Celebrex. The results indicated that Celebrex was not associated with thromboembolic events, even in the patients who did not take the low dose aspirin. The Celebrex did not show superior results for the GI profile than did the NSAID comparators, ibuprofen and diclofenac. Thus further testing will be required on this matter.
Vioxx, the trade name for rofecoxib is an inhibitor of cyloxygenase-2 or COX-2, an enzyme in the body believed to be at the root of pain and inflammation. This non-steroid anti-inflammatory drug (NSAID) is approved for relief of signs and symptoms of osteo-arthritis, the management of acute pain and for the treatment of dysmenorrhea. It is comparable to other NSAID, but has a narrower range of side effects, especially lower incidence of GI effects.
Many researchers are becoming more aware of the possible side effects that occur when COX-2 inhibitors are used by patients suffering from rheumatoid arthritis. COX-2 inhibitors caused fewer stomach ulcers than many other pain relievers, but as they have had a higher, though relatively low, risk of heart attacks than patients taking the older pain relievers. Several doctors said that they are worried about the possibility of heart attacks because many of the arthritis patients taking the drugs are elderly, and have a higher risk of cardiovascular problems to begin with. Thus we come back to the same question as to whether or not aspirin should be used in connection with COX-2 inhibitors?
In addition some new research seems to give further support to the theory that people who take aspirin regularly to reduce the risk of heart attack may also be substantially extending their lives. Dr. Patricia Gum of the Cleveland Clinic led the study group that found that in addition to reducing the risk of heart attack those individuals who took an aspirin every other day seemed to also benefit by extending their longevity.
The results of the study appeared in The Journal of the American Medical Association. The study evaluated 2,310 people who were taking about one aspirin daily or every other day at test time, and 3,864 who were not taking any aspirin at all on a regular basis. The average age of the aspirin using group was 62, while the average age of the non-users was 56. There was a total of 276 deaths in about three years of follow-up. There were about an equal number of total deaths in both groups, but since the aspirin using group was an older grouping to begin with, the researchers found that the aspirin users were 33% less likely to die than those who were not taking aspirin.
The September 4, 2001 edition of the N.Y.Times has an interesting 1 1/3rd-page ad from Boehringer Ingelheim Pharmaceuticals, Inc.with the bold headlines of the ad reading "Attention Vioxx and Celebrex Users: Are You Dissatisfied? If so, ask your doctor about MOBIC(meloxican). It's the osteoarthritis medicine with proven safety and efficacy used by 45 million patients in 100 countries for over five years." The ad contains a coupon for a free 30 day supply of MOBIC when presented to a participating pharmacy along with the coupon and a prescription for MOBIC. Thus, by innuendo, the ad seems to attack both Vioxx and Celebrex, while at the same time telling the reader to ask his/her physician for a prescription for MOBIC. How many readers will notice that this drug deals with osteoarthritis versus the rheumatoid arthritis that Celebrex and Vioxx are aimed at.
Pharmacia released Phase III data on parecoxib (COX-2 inhibitor) at the American Pain Society meeting. Results showed that the administration of parecoxib sodium, the first investigational injectable COX-2 specificanalgesic, significantly reduced the amount of morphine consumed by patients while improving overall pain relief.
Searle is presently testing Celebrex in people with a form of genetically based colon disease called FAP (familial adenomatous polyposis). The FDA has put this test on a fast track basis meaning that they will announce their decision within 6 months. Scientists have determined an extremely excessive amount of COX-2 in patients with not only colon cancer, but also in patients with pancreatic cancer and head and neck cancers.
A key advantages of the new COX-2 inhibitors is that they relieve the pain from arthritis with less risk of causing or irritating ulcers associated with the older anti-inflammatory drugs such as ibuprofen and suilind ac. Vioxx was launched in the U.S. about 5 months later than Celebrex. It accounted for about $373 million in revenue in 1999. Celebrex generated about $1.5 billion in sales in its first year, making it the best selling first year prescription drug. Although these new drugs cost about $750 per year more than generic anti-inflammatory drugs they have been deemed more appropriate for the elderly patients who have a higher risk of ulcers.
FOR AN INFORMATIVE AND PERSONAL ARTICLE ON PRACTICAL SUGGESTIONS WHEN SELECTING A NURSING HOME SEE OUR ARTICLE "Selecting a Nursing Home"
By Allan and Harold Rubin
updated February 19, 2014