Macular Degeneration Update
(10/10/12)- The Nobel Prize for Physiology or Medicine was won by John B.Gurdon of the United Kingdom and Shinya Yamanaka of Japan for their groundbreaking work in cellular reprograming.
Their work is intriguing for the possibility of treating diseases using a patientís own cells. It demonstrated that you could take mature cells from an individual that could be changed to an embryonic-like state in a laboratory dish.
It led to the first cloned animal, a frog, and to the first cloned mammal, Dolly, the sheep.
Japanese drug researchers will use this methodology to test it on retinal cells that will be transplanted into patients with macular degeneration. Dr. Gurdon removed the DNA from a frog egg and replaced it with the DNA of a mature cell taken from a tadpole. The egg developed into a healthy, cloned tadpole
(5/6/12)- The results of a two-year study that was funded by the National Eye Institute, which is part of the National Institutes of Health, reinforced the conclusion of the inspector general of the Department of Health and Human Services, as shown in our item dated 9/18/11, that Avastin and Lucentis are about equal at preserving vision in elderly people with "wet macular" degeneration,
There was a higher rate of complications in patients taking the Avastin than there were in those taking Lucentis.
Avastin costs about $50 a dose, whereas Lucentis costs slightly less than $2,000 a dose. In 2010, Lucentis was the single largest expenditure in the pharmaceutical budget of Medicare Part B, which covers certain injectible and biological drugs in the U.S.
Results of the first year of the study were published last May. The two-year results were recently published in the journal Ophthalmology.
Rates of death, heart attacks and strokes did not differ among patients taking the two drugs for their illness. Other "serious adverse events", including infections and gastrointestinal disorders, occurred at a 40% rate for patients receiving Avastin and a 32% rate for patient receiving Lucentis.
The median age of the patients in the study was over 80, making them prone to medical problems.
As noted in our item dated 9/5/11 below, a total of 21 patients have been reported to have become blind as a result of being treated with Avastin.
(11/25/11)- Regeneron Pharmaceuticals announced that the FDA had granted the company approval to market its injectible eye drug Eylea, for the treatment of "wet" age-related macular degeneration in the United States. The company has 3 Nobel Prize winners on its board, and its chairman is P.Roy Vagelos, who formerly headed Merck &Co.
Roche's Lucentis is the only other drug that has been approved for treatment of "wet" macular degeneration, which was approved in 2006. If Eylea is approved for marketing in other countries, Bayer HealthCare will market it, and the companies will split the profits.
Eylea is slightly less expensive at $1,850 an injection, than is Lucentis which costs $1,950 an injection. Please keep in mind that Genentech's Avastin costs only $50 a shot when used off-label to tract macular degeneration. Also see our item dated 9/18/11 that discussed the recent contamination problem that has been encountered in connection with the usage of Avastin.
The FDA has revoked its approval of Avastin for breast cancer, based on studies that failed to show that the drug extended the life of breast cancer patients. Avastin usage will stay on the label for colon, lung, kidney and brain cancers. Doctors may continue to prescribe Avastin, but it is conceivable that insurers will no longer be required to pay for usage of a drug for off-label purposes. Most insurers have indicated that they will continue to pay for Avastin's usage in breast cancer patients, even though it may not appear on the drug's label
The recommended dosing of Eylea, also known as aflibercept, or VEGF Trap-Eye, is once every four weeks for the first three injections followed by once every eight weeks thereafter. The label for Lucentis recommends injections once every four weeks, though many doctors inject less frequently.
Regeneron has two other applications pending approval at the FDA.-for Zaltrap, a colorectal cancer drug, and for Arcalyst, to treat gout.
The company's cholesterol-lowering drug called PCSK9 represents a new class of drug in this battle.
(9/18/11)- A recent audit report from the inspector general of the Department of Health and Human Services concluded that Medicare could have saved more than $1 billion, and Medicare patients $275 million over two years if doctors treated their patients with Avastin rather than Lucentis for wet macular degeneration.
Both drugs are made by Genentech Inc., a division of Roche Holdings AG, and have the same properties. Lucentis costs about $2,000 per injection, while Avastin costs only about $50 per injection. On average, a patient receives 8 injections of Lucentis the first year of treatment, but fewer afterwards.
The two drugs are equally effective in slowing wet macular degeneration, according to a clinical study released by the National Institutes of Health this spring.
The audit covered the years 2008 and 2009. Lucentis had over $1.7 billion in sales last year. Avastin accounts for more than 60% of the injections for age-related macular degeneration for patients covered by Medicare, but it costs the government only about $40 million compared to $1.1 billion for Lucentis according to the report.
As noted in our item dated 9/5/11 below, 21 patients have been reported to have become blind as a result of being treated with Avastin. The contamination of Avastin could have occurred when the compounders, who cut the Lucentis into smaller doses that become Avastin, were negligent in performing the process.
(9/5/11)- Under the latest count, a total of 21 patients who were being treated for wet macular degeneration with injections of Genentech Inc.'s drug Avastin have been blinded as a result of the treatment.
Avastin has not been approved for the treatment of wet macular degeneration, but because of its similar properties to Genenetech's drug Lucentis, which has been approved for the treatment of the disease, and because its injection costs only about $50 an injection versus the cost of $2,000 for Lucentis, Avastin has become the much more widely used treatment off-label for the disease.
A vial of Avastin is created by compounders who divide the Lucentis into numerous tiny doses, which are then placed in a syringe for injection into the eye. This extra processing of the drug leaves room for bacterial contamination and other problems.
The 5 latest cases occurred last month at the Veterans Affairs Sepulveda Ambulatory Care Center in the San Fernando Valley.
The FDA had issued a previous alert saying that at least 12 patients in Miami, treated at three clinics for wet macular degeneration with injections of Avantis, had suffered eye inflammations. All the infections involved a single lot of Avastin, and had been traced to a single pharmacy in Hollywood, Fla. that had repackaged the drug.
Four patients in Tennessee had received shots contaminated by bacteria that had been prepared in the pharmacy of the V.A. hospital in Nashville.
(7/5/11)- In several of our items below, including the one dated 5/2/11 we wrote about the fact that Genentech Inc.'s Avastin has been effective in fighting wet age-related macular degeneration. In a series of 6-0 votes, an advisory panel of the FDA voted to revoke the agency's prior approval for the drug's treatment against advanced breast cancer.
The panel members voted that the drug was neither safe nor effective. It also rejected a proposed compromise offered by Genentech, that the approval remains in place while the company conducts another clinical trial to try to confirm that the drug works.
The commissioner of the FDA, Dr. Margaret A. Hamburg, will make the final decision on the matter. She does not have to follow the advice of the panel.
Avastin will remain on the market as a treatment for several other types of cancer, so doctors could use it off-label to treat breast cancer, but insurers might not be willing to pay for its usage against breast cancer which runs about $88,000 a year.
Avastin is the world's best selling cancer drug, with sales last year of about $7 billion. Early indications from Medicare officials indicate that it will continue to pay for the drug's usage by Medicare and Medicaid beneficiaries.
(6/24/11)- Food and Drug Administration reviewers confirmed that they would recommend approval of Regeneron Pharmaceutical's wet age-related macular degeneration drug VEGF Trap-Eye. If approved by the FDA, Germany's Bayer AG would market the drug outside the U.S. The advisory panel than did recommend approval of the drug for sale which if approved by the FDA should begin by August 20.
The FDA based its review on a company-funded study that compared the drug to Roche Holding AG's Lucentis. VEGF Trap-Eye is designed to be administered about every two months, compared with monthly injections of Lucentis. It is administered by direct injection into the eye.
(5/2/11)- The results of a federal study that compared the effectiveness for the treatment for age-related wet macular degeneration of Genentech Inc.'s more expensive drug Lucentis, with its less expensive drug Avastin, indicated that both drugs had just about the efficacy in delaying blindness among patients with the disease.
Genentech Inc., a unit of Roche Holding AG, counterclaimed that the results of a study that it had funded showed that Lucentis was a safer drug than was Avastin.
Lucentis which has been approved by the Food and Drug Administration (FDA) for the treatment of wet macular degeneration costs about $2,000 per treatment, while Avastin, which is basically a twin drug to Lucentis costs about $50 per eye treatment. It is perfectly legal for doctors to prescribe Avastin for off-label usage of this drug for the treatment of wet macular degeneration.
The result of the study that was conducted by the National Eye Institute, a subsidiary of the National Institute of Health was published in a recent edition of the New England Journal of Medicine. It involved 1,200 patients, while the study of 78,000 Medicare patients that was funded by Genetech was conducted by researchers led by Dr. Emily Gower at Johns Hopkins University.
According to an abstract released earlier this month, the Johns Hopkins study showed an 11% higher risk of an overall mortality and higher risk of hemorrhagic stroke for those taking Avastin.
According to the American Academy of Ophthalmology Avastin now accounts for about 60% of all injections for wet macular degeneration. Lucentis cost Medicare $537 million in 2008, whereas Avastin cost about $20 million, according to a study by ophthalmologist Philip Rosenfeld of the University of Miami School of Medicine.
Data from the National Health and Nutrition Examination Survey showed the rates of age-related macular degeneration among Americans age 40 and older declined from 9.4% in the 1988-1994 period to nearly 6.5% in the 2005-2008 period. The decrease might be a result of changes in smoking rates, diet, physical activity and blood pressure, the researchers said in the Archives of Ophthalmology study.
(12/1/10)- There may be a new drug available in the battle against macular degeneration if all works out well for Regeneron Pharmaceuticals' new experimental drug called VEGF-Trap-Eye. The drug is injected every eight weeks, unlike Genentech's Lucentis, which must be injected every month.
The results of two clinical trials of the drug showed that it was as effective as Lucentis in halting macular degeneration, which is the leading cause of blindness in the elderly. Regeneron and its partner, Bayer, said they planned to apply for approval of the drug in the first half of 2011
The two similar trials involved a total of 2,457 patients who were randomly selected to receive either Lucentis every four weeks, VEGF-Trap-Eye either every, four weeks or every eight weeks The eight week group did receive the first three doses every four weeks.
About 95% of both groups in the VEGF study maintained their vision after one year, meaning their ability to read an eye chart declined by no more than 15 letters, or three lines. Regeneron said the two drugs were equally safe.
Both VEGF and Lucentis block a protein called vascular endothelial growth factor that causes blood vessels to grow and leak into the eye.
(11/16/10)- A recent article that appeared in the New York Times, entitled "Secret Rebates Offered on Costly Eye Drug" by Andrew Pollack, alleges that the Swiss drug company Roche Holding's subsidiary Genentech began, on October 1, offering rebates to ophthalmologists who used the companies more expensive drug Lucentis, rather than its cheaper drug Avastin to treat macular degeneration..
Under the program the doctors would receive the rebates if they used a certain quantity of Lucentis, and if their usage increases from the previous quarter, "according to a confidential document outlining the program obtained by the New York Times."
Lucentis was approved for the treatment of macular degeneration in 2006, and costs about $2,000 for each injection, with an injection into the eye needed as often as once a month.
Genentech's other drug Avastiin, was approved for the treatment of certain cancers, but many eye doctors say it works as well as Lucentis does for the treatment of macular degeneration. It costs only about $20 to $50 per usage.
Rebates are considered a form of volume discount, and are legal if they adhere to certain guidelines.
Medicare reimburses at 6% above the average selling price of a drug, so that a doctor receives substantially more for using Lucentis rather than Avastin. The preliminary results of a clinical trial, sponsored by the National Eye Institute, comparing the results of the two drugs on patients with macular degeneration is expected before the end of the year.
(5/4/10)- The results of the first year of a three year study involving the drug Lucentis for the condition known as diabetic macular edema were quite positive according to an article that was published in the online edition of the Journal Ophthalmology.
The National Eye Institute that is part of the National Institutes of Health is sponsoring the trial. It was funded by Genentech, which is the manufacturer of the drug, and funded by a $9 million grant from the company. Genentech supplied the drug Lucentis for the trial, and specifically required that drug, rather than its other drug, Avistin, be used for the test.
Although it is approved for use in connection with the treatment of cancer, Avastin has the same properties as does Lucentis but is much cheaper to use. Lucentis costs about $20 to $100 per use, while Lucentis costs about $2,000 per injection.
The trial involved 691 patients, some of whom had both eyes treated, resulting in 854 total eyes.
Nearly 50% of the patients treated with Lucentis, often in combination with standard laser therapy, had an improvement in vision of at least two lines on an eye chart after one year. This compared with only about 30% of those receiving laser therapy alone.
Dr. Frederick L. Ferris III clinical director of the National Eye Institute, the sponsor of the trial, said that at least one million Americans now have diabetic macular edema, and that number is expected to grow as diabetes continues to grow in this country.
The condition is one consequence of diabetic retinopathy, which is the leading cause of blindness in working-age Americans.Dr. Neil M. Bressler of Johns Hopkins University is the chairman of the group conducting the trial.
Please see our items dated 10/30/09 and 10/7/09 for more on the topic of Lucentis versus Avastin
(10/30/09)- The Centers for Medicare and Medicaid Services (CMS) announced that it planned to increase the payment to eye doctors who use Genetech Inc.'s Avastin for the treatment of macular degeneration. For additional details on this matter, please see our items dated 10/7/09 and 12/25/07 below.
The increase would be effective no later than January 1, 2010.
Both Avastin and Lucentis are made by Genetech, with the former drug costing about $50 when used for eye-disease injections, while the latter costs about $2,000 per injection.
The October payment ruling re Avastin meant that eye-doctors would only be reimbursed $7.20 when using that drug, and this was less than the amount that Genetech charged the physician for the drug.
Currently, about half of all doctors use Avastin to treat macular degeneration.
(10/7/09)- For several years, eye doctors have used Genetech's cancer drug Avastin to treat age related macular degeneration. The drug is similar to Genetech's other drug Lucentis. Lucentis costs about $2,000 per injection, while Avastin, when used in the tiny portions required for the treatment of macular degeneration costs only about $30 to $50 per shot.
Medicare officials recently introduced a special lower reimbursement rate for the smaller dose injections of Avastin of $7.20. The new payment would therefore give eye doctors a financial incentive to switch to Lucentis, for which they would be receiving a higher reimbursement. In turn this would result in a higher cost to Medicare.
Dr. David W. Parke II, chief executive of the American Academy of Ophthalmology stated: " Members view this as a bureaucratic decision that is maybe necessary, based on statutes, but highly short-sighted."
(4/29/09)- Nearly 15 million people suffer age-related macular degeneration (AMD), and 1.7 million of them suffer from an advanced form of the disease. The disease is part of the normal aging process, and results from damage to the macula, the portion of the eye that is responsible for central vision and the ability to see fine details clearly. Risk factors include smoking and family history.
AMD initially affects the patient in one eye and, over time, has a high probability of occurring in the second eye.
Wet AMD accounts for approximately 90% of all AMD-related blindness. All cases of AMD begin first as the dry form, but 10% to 20% progress to the wet form. There are about 200,000 new cases of the disease diagnosed each year.
There are no treatments that have been approved by the FDA for the dry form of the disease. It progresses more slowly than the wet form, and can cause severe loss of central vision or legal blindness in 15% to 20% of people afflicted.
(12/25/07)- Genetech Inc. and two societies of eye doctors announced that doctors would be allowed to purchase Avastin themselves and have the drug delivered to compounding pharmacists so that they could use the drug for the treatment of macular degeneration. Please see our item dated 12/6/07 below.
As we point out Genetech's Lucentis and Avastion are basically the same compound. Lucentis is approved for the treatment of macular degeneration and costs about $2,000 for each injection. Avastin is not approved for the treatment of macular degeneration but it only costs between $20 to $100 per injection for smaller dosages.
Under the agreement Genetech would not have to sell the drug directly to the compounders starting January 1, 2008. The two eye societies involved in the matter are the American Academy of Opthalmology and the American Society of Retina Specialists.
The agreement also called for Genetech to improve its programs for helping patients pay for Lucentis, or to find ways to provide it free to those who cannot pay for it. The company would also work to expedite reimbursement to doctors, who generally buy the Lucentis themselves and must wait to recover outlays from patients bills or their insurers.
(12/6/07)- Genetech Inc.'s plan to restrict the sale of Avastin, as we note in our item dated 10/17/07, has been criticized by Senator Herb Kohl, Democrat of Wisconsin. According to the senator's numbers, this restriction could cost taxpayers anywhere from $1 billion to $3 billion a year in increased Medicare and Medicaid costs, in addition to which its total cost to the consumer would also be in the billions of dollars.
In a letter that Senator Kohl sent to the Centers for Medicare and Medicaid Services, to the FDA and to Genentech he states that the company's decision to restrict the access of Avastin from companies that repackage drugs "is of great concern."
In his letter to Genetech he went on to inform the company that his staff would investigate the restriction. As we explain in the earlier item, the company's newer drug Lucentis is much more costly than the earlier generation of the drug Lucentis, which are used to treat macular degeneration.
(10/17/07)- Genetech Inc. announced that it's wholesalers would restrict the sale of Avastin to compounding companies, as the company attempts to prevent increased usage of that drug in place of its other drug Lucentis in the battle against macular degeneration. For more info on this topic please see our items dated 1/28/07, 10/10/06 and 7/7/06 below.
Lucentis had been approved by the FDA to treat wet macular degeneration (which is the most common cause of macular degeneration) in June 2006, but it costs about $2,000 a dose, with treatment needed as often as once a month. On the other hand Avastin, when injected into the eye in tiny amounts, costs about $50 a dose.
Avastin has the same chemical properties as does Lucentis, and as we point out in the item dated 10/10/06 the National Eye Institute is sponsoring a trial that will directly compare the two, but the results won't be known for several years.
In a letter that Genentech sent to retina specialists, the company said that its wholesalers would no longer provide Avastin to compounding companies. Compounding companies are the ones who in turn divide a vial of Avastin into tiny portions for use in the eye. The company said the distribution change would take effect November 30. The company claims that the possibility exists for microbial contamination when the compounding companies cut the drug into smaller portions.
Of course it still is possible for eye specialists to buy Avastin themselves, and then send it on to a compounding company, but in doing so you would be adding an additional cost ultimately to the patients.
(1/28/07)- Genetech Inc posted a letter on its Web site that it had sent to retina specialists in which it warned them that recent research indicated that a study that it was conducting indicated that high dosages of its macular degeneration drug Lucentis increased the risk of stroke. This new finding raises questions about the risk of Avastin, the company's cancer drug which is used off-label for treating macular degeneration at a much lower cost than Lucentis.
Lucentis, also called ranibizumab, was approved in June 2006 by the FDA to treat the wet form of macular degeneration. It is the first drug shown in clinical trials to improve eyesight for a significant number of patients with the wet form of macular degeneration, as opposed to the other drugs, which merely slow the progression of the disease.
The drug's label already contain a warning about the increased risk of blood-clotting events like strokes.
According to the letter, 1.2% of patients treated with the high dose of Lucentis in the clinical trial suffered a stroke, compared with only 0.3% for those treated with a low dose.
The study involves 2,400 patients who have been followed for an average of 230 days since beginning treatment. The study will continue for at least a year.
A high dose injection of Lucentis is 0.5 milligrams per injection. The drug had sales of $380 million for the 1/2 a year that it was on the market in 2006. For more on Lucentis and Avastin see our item immediately below this one.
(10/15/06)- The FDA has approved Genetech Inc.'s Avastin's for the treatment of nonsmall-cell lung cancer, in addition to its approval for the treatment of colon cancer. Please see our items dated 10/10/06 and 8/12/06 for Avastin's usage in connection with the wet form of macular degeneration.
Avastin is designed to starve tumors of blood and nutrients. The drug is used in conjunction with chemotherapy for the treatment of lung cell cancer. Avastin costs about $4,400 a month for treatment of colorectal cancer, but about twice as much of the drug is used in connection with the lung cancer treatment.
The drug, which is also known by its chemical name as bevactizumab, prolongs the life of lung cancer patents along with the chemotherapy for about two months, according to the main clinical trial. Those who got Avastin along with two chemotherapy drugs had a median survival of 12.3 months compared with 10.3 months for those who got only the chemotherapy.
Genentech has also announced that it would cap the total cost of the drug at $55,000 a year for patients below a certain income level. That $55,000 cap would be for total spending by all payers, including Medicare, private insurers and the patient. The company has not decided yet what the income level would be, but it is expected that it will be in the $75,000 range.
Approval was based on a study showing Avastin and chemotherapy resulted in a 25% improvement in survival compared with chemotherapy alone. Susan Desmond-Hellman, head of product development at Genetech, said the lungo-cancer approval would make another 65,000 to 81,000 patients candidates for the drug.
(10/10/06)- The National Institute of Health announced that it would fund a study that would compare two of Genetech Inc.'s drug in connection with the treatment of age related wet macular degeneration. For some additional information on this topic please see our item dated 8/12/06. The two drugs that will be evaluated in the study are Avastin and Lucentis.
The more expensive drug, Lucentis, was approved for use in treating the disease in June, but it costs roughly ten times as much as does Avastin. Lucentis is the first drug that has been shown to improve vision in people suffering from the disease.
The wet form of age related macular degeneration is characterized by abnormal leaky blood vessels that form under the retina, the light-sensing part of the eye. The vessels then leak fluid into the eye, damaging the macula, the central part of the retina at the back of the eye.
Novartis AG and Genentech developed Lucentis. Switzerland-based Roche Holding AG is the majority owner of Genentech, which sells the drug in the U.S. Novartis sells the drug throughout the rest of the world. The only other drugs approved by the FDA to treat macular degeneration are Pfizer's Macugen and OSI Pharmaceutical Inc.
Both Lucentis and Avastin work in the same way in treating the disease. It is estimated that there are about 200,000 new cases of wet AMD each year in the U.S.
The National Eye Institute, which is a part of the National Institutes of Health, said that it would fund the study since Genentech felt that there was no need for such a study.
The trial will cost about $16 million and involve 1,200 patients, who would be divided into 4 groups. One group would get Lucentis every four weeks and another group would get Avastin at that same interval. The other two groups would get either of the medications on an as needed basis rather than at set intervals.
The patients will be followed for two years, but the study would take four years. Maryann Redford would be the administrator of the study. She said that cost savings was not the primary reason in her mind for the study.
(8/12/06)- Thanks to our viewer Kevin Stenson for pointing out the error in our item dated 7/7/06. The item as originally written said that Lucentis cost about one-tenth the price of Avastin, when in fact it should have read, as it now does as emphasized in red, "ten times".
(7/7/06)- Genentech's Lucentis is the first drug demonstrated in clinical trials to improve vision in people with wet-macular degeneration, has received approval from the FDA. As our item dated 10/7/05 points out, this drug is a derivative of Genentech's Avastin, which has been approved only to treat cancer. Avastin works the same way as Lucentis does to treat wet-macular degeneration.
Genentech has no interest in getting Avastin approved for macular degeneration, because that would undermine the sales of Lucentis, which sells for about ten times the price of Avastin. Genentech is majority-owned by Roche Holding AG of Switzerland. Swiss-based Novartis AG was also involved in the development of Lucentis.
FDA approval for Lucentis was granted under the agency's expedited priority-review process, which cuts about 4 months off the typical 10-month drug-review period of time. The company will begin shipping the drug immediately.
Avastin costs about $50,000 a year to treat cancer, but for an injection into the eye to treat macular degeneration, only about $20 to $100 worth of the drug is needed. Lucentis will cost $1,950 per injection. An injection is needed as often as every four weeks for both drugs.
Both drugs work by stopping the growth of new blood vessels, which in turn means that the leakage of the blood vessels is sharply retarded. In clinical trials one-quarter to one-thirds of patients who received Lucentis gained three or more lines of vision on an eye chart, benefits that have lasted two years so far with continued injections.
About 40% of the patients ended up with at least 20/40 vision, and only 10% had a degradation of vision of at least three lines on the eye chart after two years. About 15 million Americans have age-related macular degeneration, and roughly 10% if those suffer from the wet-form of the disease.
(4/7/06)- The Carver Charitable Trust has donated $10 million to the University of Iowa's Center for Macular Degeneration. Five million dollars of the donation will go to the John and Marcia Carver Nonprofit Genetic Testing Lab at the university, and the other $5 million will go to endow two chairs there.
Roy J. Carver founded Bandag, a tire-retreading business in Muscatine, Iowa. After he died in 1981 his son Martin became chief executive of the company. Martin's wife Ruth's family discovered 60 years ago that they were susceptible to Best's disease, an eye condition related to macular degeneration.
(1/5/06)- In an eight-year study of more than 4,000 older residents of Rotterdam, the Netherlands, researchers determined that a vitamin-rich diet lowers the risk of contracting macular degeneration among the elderly. The antioxidant properties of Vitamin C and E, beta-carotene and zinc were found to ward off macular degeneration.
Taking of these vitamins slows the progression of this disease, it does not cure it.
(10/7/05)- Genentech's Lucentis, which is a drug that has shown promise in reversing the effects of age related macular degeneration is a derivative of its drug Avastin. Genentech still has not announced the price that it will be selling the intravenously administered drug, but it is expected to cost in the same range as is Macugen which goes for about $1,000 an injection. Pfizer and Eyetech Pharmaceutical sell Macugen.
Avastin is an expensive drug since it costs about $4,400 a month for colorectal cancer patients. Doctors however are prescribing Avastin for off-label usage in fighting age related macular degeneration. To help keep is cost down, the physicians are having pharmacists divide the vials of Avastin into tiny portions, so that the amount needed for each injection costs only about $30 to $100.
Both Lucentis and Avastin block a protein in the body that spurs development of blood vessels. In doing so it can choke off the blood supply to cancerous cells. In macular degeneration, Lucentis dries up leaky blood vessels that accumulate in the back of the eye and damage the macula, the central part of the retina.
Genetech recently began to recruit 5,000 patients to teat Lucentis at no cost to further test the drug's effectiveness in dealing with age related macular degeneration.
(7/27/05) Age related macular degeneration is associated with thickening of the retina. Last month, Sima Therapeutics (Boulder CO) presented the first ever clinical data for an RNAi-based drug in on ongoing phase I trial for age-related macular degeneration (AMD). The objective of this drug is to degrade the messenger RNA from its target gene, thus preventing the expression of the gene for macular degeneration. The researchers have treated 14 patients with single, intravitreal doses of the drug, called at this time, sima-027. Visual acuity was tested after 84 days, with indications of a dose dependent trend of improvement in terms of numbers of letters read on the eye chart and a reuction of retinal thickness.
There are indications that this class of drugs may be helpful in other conditions including HIV, respiratory synctial virus infection, avian infection, and many variations of the flu virus. Final evaluation of this drug class is still a long way off.
(7/25/05)- Genetech released further details of the results of its MARINA trial at a meeting held in Montreal of the American Society of Retina Specialists. The results of the study continue to be very encouraging in the battle to improve vision for patients who have the wet form of macular degeneration.
Patients in the clinical trial with macular degeneration who received Lucentis had an average gain of 7 letters on a standard eye chart compared with a 10.5 letter loss of those given a placebo. Macular degeneration continues to be the leading cause of blindness for people over the age of 65 in this country. The Swiss company Novartis will have marketing rights for sale of the drug outside North America.
(5/31/05)- Genentech announced the first year results from its phase III MARINA study of its drug Lucentis for the treatment of wet macular degeneration. It appears that the drug is effective in not only preserving vision for those who have the disease, but it also improved their vision also. All other drugs used in the treatment of wet macular degeneration have only been effective in preserving, not improving, vision loss.
There are about 200,000 cases of the wet form of the disease diagnosed in the U.S. according to Eyetech Pharmaceuticals, the seller along with Pfizer of Macugen. The only other drug that has been approved for treatment of the disease is Visudyne, from QLT and Novartis.
The MARINA study enrolled 716 patients with minimally classic or occult wet AMD (age-related macular degeneration). It is designed as a two-year study, so there will be more data coming in the future on the study. MARINA is a double-masked trial aimed at determining the safety and efficacy of Lucentis (ranibizumab) at 0.3mg or 0.5mg dosages injected once a month compared to sham injections. Macugen requires injections every 6 weeks as opposed to the 4-week time interval required for Lucentis injections.
The results demonstrated that 95% of the patients who were treated with Lucentis maintained or improved their vision, compared with 62% of the patients who received the sham injection. This compares to Phase III results of Eyetech/Pfizer's 0.3-mg dosage of Macugen which demonstrated that 70% of the patients maintained or improved vision in the VISION study. Lucentis was well tolerated by the patients who received the injection with the most common adverse effect being conjunctival hemorrhage, eye pain and vitreous floaters. Novartis will sell the drug outside the U.S., once approval has been gained from the FDA to sell it.
Genentech did not report the percentage of people with an improvement of at least three lines on the eye chart, an amount considered meaningful in patients. The company expects to report the results of a second trial on the drug in the fourth quarter. That phase III study, which is known as ANCHOR compares Lucentis to photodynamic therapy (PDT) by Visudyne. The detailed results of the first year MARINA study will be presented at the American Society of Retina Specialists (ASRS) on Monday, July 18th in Montreal Canada.
Macugen received regulatory approval in December 2004 from the FDA. Genentech estimates that over 15 million people have AMD in the U.S., consisting of 1.4 million with the wet form and 13 million with the dry form.
(3/16/05)- Scientists involved in three different, and independent of each other, studies have identified a genetic variation that substantially increases the risk of age related macular degeneration (AMD). AMD is the leading cause of severe vision loss in the elderly.
The variation, a change of a single unit of DNA out of the three billion units that make up the human genetic blueprint appears to be common in the study subjects. The more common form of the disease is the dry one. The two drugs that are available to treat the wet form of the disease (which is the more serious form of the disease) can only retard the progress of the disease, they can not cure a patient of the problem.
Researchers feel that the variant may account for between 20% to 50% of those who are at risk for the disease. The variant is not an absolute determinant as to who will get the disease. Previous studies have shown that smoking or being obese raises the risk of macular degeneration. On the other hand eating leafy green vegetables, certain vitamins and zinc can lower the risk of getting the disease.
The change in the DNA letter led to a change of a single amino acid in the protein, complement factor H. Complement factor H acts as a brake on the immune response and inflammation. The variant form of the protein may be a less effective brake. Scientists cautioned that there is not enough evidence available for people to go out and get tested if they have the variant of the gene.
(1/5/05)-The FDA has approved Macugen for the treatment of the wet form of macular degeneration that we discussed in this article dated 10/29/04. Pfizer Inc. will market the drug in conjunction with Eyetech Pharmaceutical, the company that developed the drug. The wet form of age related macular degeneration (AMD) occurs when abnormal blood-vessel growth harms or destroys part of the eye. It is the less common form of the disease, but causes the most cases of severe vision loss.
Part of the study seems to show that patients benefit the longer they are on Macugen as measured by "events", or the loss of three or more lines on a vision chart. Patients receiving Macugen for one year had 35 events, compared with 21 events for the group that received the drug for two years. The drug is injected into the patient's eye every 6 weeks. Please keep in mind that Macugen is not a cure for macular degeneration, it just retards the onslaught of the loss of sight in the patients who receive the drug.
(11/22/04) An experimental new drug for the treatment of macular degeneration has shown itself to be promising in regards to improving vision rather than just holding back the negative effects of the disease. Genentech Inc. of South San South San Francisco, California developed the drug, Lucentis. It is designed to block a protein that plays a critical role in the formation of new blood vessels. The drug still has a long way to go before it can be approved for public usage. Results of the small study group were presented at the American Academy of Ophthalmology's annual meeting in New Orleans in September.
Worldwide sales of Visudyne are expected to be about $450 million for Novartis AG, which has the marketing agreement for the drug with QLT Inc. of Canada. Pfizer Inc. will do the marketing for Eyetech's Macugen. Alcon Inc.'s macular degeneration drug Retaane has come up empty handed so far, since the drug seems to leak out of the eye before its effects can be felt against the disease. Macugen and Lucentis are injected directly into the numbed eyeball of the patient, while Retaane is injected into the side of the eye.
(10/29/04) New data presented at the same American Academy of Ophthalmology meeting in New Orleans showed that a study of the patients receiving Eyetech's drug Macugen experienced less vision loss that those on a placebo after two years. Macugen is designed to treat the wet form of macular degeneration, which is the less common form of the disease AMD. AMD is the leading cause of blindness in Americans age 50 or older.
An advisory panel (Dermatologic and Ophthalmic Drugs Advisory Committee) had ruled unanimously that Eyetech had produced enough information to evaluate its drug Macugen ™ for the treatment of "wet" macular degeneration. This is the less common form of the disease that afflicts an estimated 1.6 million Americans, with over 200,000 new cases being diagnosed each year.
The panel members did not seem to raise any serious new issues that would block approval. The FDA is now scheduled to make a decision on the drug by mid-December. Jennifer D. Harris, the lead reviewer of the drug for the FDA told the advisory panel that the drug "does reduce the risk of vision loss", but that there was no "clinically meaningful" improvement in vision.
The biggest concern of the panel members was that 2% of the patients in the clinical trial developed potentially serious eye infections. That is because the drug is given by an injection directly into the eye every six weeks. Some of the panel members said that more study is needed about the long term effects of the treatment since the protein blocked by the drug, vascular endothelial growth factor has positive effects, like spurring the growth of valuable blood vessels in the body.
The study was based on 1,953 patients who were followed for two years. Those receiving Macugen suffered an average loss of 9.4 letters, as measured on an eye chart, as opposed to those receiving a "sham" injection who lost an average of 17 letters. Dr. Donald J. D'Amico, an ophthalmology professor and practitioner at the Harvard Medical School, who is overseeing a safety monitoring committee for Macugen, said early studies showed 16 cases of serious eye infection out of more than 8,000 injections. The company then changed the injection procedure and the number of serious infections fell to two out of more than 6,000 injections.
Up until now there is only one FDA-approved medicine on the market for treating wet AMD, namely Visudyne, which is marketed by Novartis AG (NVS) and QLT Inc. Visudyne is injected into the arm of the patient and then followed up with a laser procedure. Several other companies are developing drugs to treat AMD including Genentech Inc., Genaera Corp,, and Alcon Inc.
Eyetech Pharmaceutical Inc. and Pfizer Inc. announced that they have completed the filing of a New Drug Application (NDA) with the FDA for Macugen ™ for the treatment of wet-age-related macular degeneration. This disease is the leading cause of severe vision loss in patients older than 50 years of age in the developed world.
Pfizer Inc. is an investor in the company and will market the drugs after it has gained approval from the FDA. Pfizer paid a $75 million licensing fee for Macugen and invested $35 million in Eyetech. Pfizer has agreed to invest up to an additional $25 million in Eyetech over the next several years. Pfizer bought $10 million of the stock when the issue went public in January 2004.
Data for the results of the Macugen study were presented at the conference for the American Academy of Ophthalmology. The study showed that Macugen improved or stabilized vision in 33% of the 1,200 patients tested compared with the 23% of the placebo group that reported the same result.
A very small 64-patient trial of patients with macular degeneration, of a drug rhuFabV2 has resulted in the improvement of at least three lines on an eye chart after three months for 26 % of the patients in the study group. Obviously the small group of patients involved in the trial is not enough of a sampling to be considered significant, but it is a step in the right direction. It may also be leading to false hope, since the study has not determined the long term effect of the drug.
The drug was developed by Genentech, the biotechnology company from South San Francisco, Ca., but it appears to work only in people with newly diagnosed cases of the disease. It does not work with people who have had the disease for a long time. RhuFab is for the wet form of the disease, but is not successful for the more common dry form of the disease. There are about 200,000 new cases of the wet form of macular degeneration diagnosed each year in the U.S.
Another drug, Anecortave Acetate, developed by Alcon Laboratories of Fort Worth is in final-stage trials for treatment of macular degeneration. The drug has been in trial for about a year, and about 12% of treated patients showed an improvement in vision of two lines or more. This drug is also only for patients who have the wet form of the disease.
Three Medicare beneficiaries and three advocacy groups have sued Medicare for wrongfully denying them the opportunity to appeal Medicare's decision not to cover their Visudyne treatments for the "occult" type of the wet form of macular degeneration. The three advocacy groups that have joined the suit are: the American Council of the Blind; the Gray Panthers and the American Association of People with Disabilities.
The plaintiffs in the lawsuit claim that CMS failed to abide by the law passed in 2000 that required the agancy to set up an appeals process for denial of coverage decisions. In the past, CMS have stated that they won't implement an appeals system until Congress provides funding for the process. The law that was passed in 2000 that required the setting up of the appeals process failed to provide any means to finance the appeals process at Medicare.
About 5 % of Americans over 65, or 1.7 million people have macular degeneration. Most people have the "dry" form for which there is no treatment. The other form of the disease is the "wet" form, which afflicts about 10% of those who have the disease. The "wet" form is caused by abnormal blood vessels, called lesions. Laurie McGinley wrote an article in the Wall Street Journal entitled "Medicare Flip-Flop On Eye Drug Roils Elderly Victims", that tells the story of how Medicare reversed itself in connection with coverage for drug Visudyne for the "occult" type of the wet form.
In the occult for of the disease the lesions grow like weeds deep in the eye and then leak. The lesions are called "classic" if the leaky blood vessels are easily detectable or "occult" if they are hard to detect. The Food and Drug Administration granted approval on April 12, 2000 for the drug Visudyne to treat " wet " macular degeneration. Medicare decided to cover Visudyne therapy for classic "wet" macular degeneration in November 2000. The drug costs about $1,230, and to that cost you then must add the doctor's fee.
In the clinical trial for patients with the occult form of "wet" macular degeneration no appreciable benefits were found for those taking the treatment for one year. The trial did show appreciable benefits for patients after 24 months. In order to be able to market the drug for occult treatment the marketers needed specific FDA approval to change the drug's label. FDA officials said that they would require more trial data to prove that the drug worked on the occult form. Approval was given for coverage by Medicare for those being treated with the occult form of the disease treatment on October 17, 2001.
When the FDA heard that Medicare had approved payment for the treatment for those who had the occult form of the disease, it notified Medicare that it considered the occult trial for the drug a failure. Medicare then reversed its decision to pay for the treatment, and that is why, as of now, Medicare will not pay for the occult treatment for Medicare beneficiaries.
QLT Photo-Therapeutics of Vancouver, Canada developed the drug, known as Visudyne. The wet form affects about 200,000 Americans each year. It is marketed in conjunction with Novartis AG's Ciba Vision unit. Visudyne (TM) therapy reimbursement in the U.S. has been expanded to include patients with occult form of wet-age related macular degeneration.
In a clinical trial involving patients with the classic form of the disease about 600 patients, or 61.4 % of those who took the drug had vision that was stable or improved after one year. It does not cure the disease, but it merely slows or halts the deterioration that the disease causes. It is to be used in connection with the wet form of the disease, which while less common than the dry form, accounts for the majority of cases of blindness caused by the disease.
In the dry form of the disease yellow deposits accumulate on the retina. About 90% of the disease are in the dry form. In the wet form abnormal, leaky blood vessels accumulate behind the retina. The dye is fed intravenously through the arm. About 15 minutes thereafter a laser beam is zapped into the eye for about 1 and 1/2 minutes. This laser beam activates the dye attached to the diseased blood vessels which in-turn seals the leaky blood vessels. The treatment costs about $2,000 and will have to be repeated for most patients every 3 months.
Ciba Vision officials stated that they had trained about 85% of the 1300 retinal specialists in this country on how to administer the treatment. About 600 of these specialists have access to the laser equipment. QLT is seeking market approval for the drug in Canada and Europe.
Unfortunately the stabilization does not appear to be permanent. It is a step in the right direction, but much more work will have to be done before we have a "cure" for this disease. Still in the testing stage are some other possible treatments such as radiation therapy, surgery and anti-angiogenesis drugs.
CMS recently announced that it intended to expand the treatment options available for Medicare beneficiaries with age-related macular degeneration, the leading cause of blindness in older Americans.
New Medicare coverage policy will expand coverage of Ocular Photodynamic Therapy with verteporfin for this eye disease. Approximately 35,000 to 70,000 beneficiaries will be affected by this new policy, tripling the number helped by this treatment.
Ocular Photodynamic Therapy (OPT), which is exclusively used in patients with wet AMD, involves the infusion of a light activated drug called verteporfin. Infusion of verteporfin is followed by the use of a non-thermal laser. Upon application of this laser, verteporfin becomes active and begins treating the adjacent lesions, resulting in the temporary closure of leaking blood vessels.
According to the latest figures about 1.7 million Americans suffer from macular degeneration. The vast majority of the 1.7 million are over the age of 60. There is presently an ongoing study involving 4,757 subjects aged 55 to 80 that is assessing the effect of antioxidants and zinc supplements on the development and progression of age related dry macular degeneration. In 1994 the National Eye Institute (NEI) reported that people with high blood levels of lutein and zeaxanthin and high dietary intakes of them, have a much lower rate of wet AMD. Lutein can be found in dark green vegetables especially kale, spinach, collard greens and broccoli. Zeaxanthin can be found in yellow and orange colored fruits and vegetables such as peaches, nectarines, persimmons and corn.
Further results of the study done by the NEI indicate that taking high dosages of dietary supplements seems to retard the progression of the disease. The dietary supplements did not prevent the onset of the disease not, did it prevent cataracts from forming. The dietary supplements used in the tests were a combination of zinc and the antioxidants vitamin C, vitamin E and beta-carotene. Among people who had significant yellowish deposits accumulating at the back of their eyes, the supplements cut the risk of vision loss by one-fith. These yellowish deposits occur during the aging process.
Dr. Frederick Ferris, director of clinical research at the NEI stated that taking the supplements helped to retard the onset of blindness as a result of the disease. It is unknown at this stage of the study whether the results obtained so far will continue to show the same effect, but the study is continuing. The daily dosages of the antioxidants used in the study were 500 milligrams of vitamin C, 400 milligrams of vitamin E and 15 milligrams of beta-carotene. The body converts the beta-carotene into vitamin A. The dosage level for the zinc was 80 milligrams with 2 milligrams of copper. These amounts are well above the levels recommended by the FDA, so individuals should consult their own physicians before they try takng the supplements on their own. Beta-carotene raises the risk of lung cancer among smokers.
Only 15 % of patients with wet age related macular degeneration (AMD) are eligible for the two available approved treatments (photodynamic therapy and laser photocoagulation). The FDA has granted fast-track status for a possible third treatment method of wet AMD called SnET2 (tin ethyl etiopurpurin). It is an investigational drug being co-developed by Miravant Medical Technologies and Pharmacia Corp.
The Phase III trials involves 900 patients with wet AMD. The patients are being treated with SnET2 and a diode laser using 664nm wavelength. As of December 1999 data was reviewed from 758 of the patients, whose mean age was 76.6 years and 58 % were females. A data safety monitoring board, which was established to review the data at three-month intervals, has not identified any significant safety issues to date. The final data will not be available till some time around the end of 2001.
Macular degeneration is divided into 2 forms, dry (atrophic) and wet (exudative). About 90% of age-related macular degeneration (AMD) is the dry form which involves the slow degeneration of the light-sensing cells in the macula. This form results in blurred central vision. The remaining 10% suffering from the wet form of macular degeneration are at much greater risk to becoming blind entirely.
In the case of the wet form of macular degeneration the blood vessels beneath the macula leak blood and fluid causing rapid damage to the central vision. The macula is about 1/4 of an inch wide, and is located in the central part of the retina. The retina is the nerve layer in your eye that senses light and allows you to see. The degeneration is caused as a result of the breakdown of the layer between the retina and the choroid (the layer of blood vessels behind the retina).
The February 17, 2000 issue of The New England Journal of Medicine contains an article "Age Related Macular Degeneration" by S.L.Fine, M.D., J.W.Berger, M.D., Ph.D., M.G. Maguire, Ph.D., and A.C.Ho, M.D. The article fully discusses the problem of macular degeneration and states: " There is no effective treatment for most patients with age-related macular degeneration, and many patients therefore resort to experimental treatments."
According to the article the prevalence of late age related macular degeneration rises to 7.1% of those over 75 years of age. The best hope right now in fighting the disease is early detection. What follows is an evaluation of the present known treatments for macular degeneration
Recently the cancer research scientific community has been exploring newer methods to kill deadly cancers without destroying healthy cells. They were looking for a selective therapeutic approach in which they could kill the target cells at different levels of the site of the cancer without harming surrounding tissue. They now believe they have developed such an approach called photodynamic therapy. A substance (usually referred to as a sensitizer) is placed in the cancer cells and by activating this substance through the use of light (usually red), it causes release of reactive oxygen which destroy the target tissue. These sensitizers show preference for accumulation in diseased tissue, reducing to minimum destruction of healthy tissue.
Using this methodology it is possible to treat several lesions simultaneously and healing without scarring has ensued. This method is able to deal with sub-clinical lesions, catching the cancer tissue at early stages of growth, limiting spread and enhancing the chances for full recovery.
Presently, this method is being used in both early and advanced pulmonary and esophageal cancer. It is also being investigated for use in malignancies of the skin, head and neck, breast and bladder and a range of non-oncological disorders including menorrhegia, age-related macular degeneration, vascular disease and psoriasis.
For further information we recommend your read:
Dougherty TJ, Gomer CJ, Henderson BW et al. Photodynamic Therapy (Review). J. Natl. Cancer Inst. 1998; 98:889-995
Macular degeneration is a part of the body's natural aging process. The process with dry AMD evolves over many years time, as the retina becomes thinner and thinner. A 1997 Senate report called AMD "the leading cause of severe visual impairment and blindness" in the U.S. It affects about 1 of every 10 Americans over the age of 65.
There is no specific treatment for macular degeneration. A zinc supplement in your diet may slow the progression of the disease, but it can not stop it entirely. Since peripheral vision is maintained you can manage to see to some degree. There is no pain. One eye may suffer worse than the other may. The telltale sign of the disease is when the center of your vision looks dark, blurry or empty. There is no known effective prevention for the disease.
The tests that are available include the following:
FOR AN INFORMATIVE AND PERSONAL ARTICLE ON PRACTICAL SUGGESTIONS WHEN SELECTING A NURSING HOME SEE OUR ARTICLE "Selecting a Nursing Home"
By Allan Rubin and Harold Rubin
updated October 10, 2012
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