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Study Aims to Clarify Efficacy, Safety of Eye Drug Treatments

Study Aims to Clarify Efficacy, Safety of Eye Drug Treatments The press release seems simple enough: “The National Eye Institute of the National Institutes of Health will fund a new multicenter clinical trial to compare 2 drugs currently used to treat advanced age-related macular degeneration (AMD).” But its ramifications are enormous. The drugs in question are ranibizumab (Lucentis) and bevacizumab (Avastin), both manufactured by Genentech Inc, of South San Francisco. Currently, only ranibizumab is approved by the US Food and Drug Administration (FDA) for treating neovascular AMD. And it works well, with more than 90% of patients reporting a halt in vision loss and about 30% reporting improved sight. But a single dose of ranibizumab costs almost $2000 (or $48 000 for a typical 2-year course of monthly treatments). Although Medicare pays for ranibizumab, it covers only 80% of the cost, meaning that patients who do not have coinsurance pay $9600 out of pocket for a 2-year course. (Genentech does provide financial assistance and a free drug program for those who qualify who cannot pay for treatment.) As an alternative, a significant number of physicians are using bevacizumab off-label for AMD treatment. It costs about $40 a dose. A new multicenter clinical trial is enrolling patients with advanced age-related macular degeneration to compare the effectiveness of the only drug approved for that indication with a much less costly alternative that is being widely prescribed off-label. (Photo credit: JAMA. 2006;295:2394-2406) Payers such as Medicare and patients who lack insurance or have copays will obviously experience huge cost savings if bevacizumab is found to be as effective as ranibizumab. Such a finding would also provide another treatment option for AMD in developing countries, where ranibizumab is generally not affordable. On the flip side, Genentech stands to lose billions of anticipated dollars if ranibizumab is abandoned for AMD treatment. But beyond Genentech, the biotech and drug manufacturing industries are concerned about the precedent created by this trial and could use their political clout in an attempt to derail the study, said William Rich III, MD, medical director of health policy for the American Academy of Ophthalmology in Washington, DC. “Obviously, biotech hates head-to-head trials based on efficacy and affecting payment,” Rich said. “I’m anticipating delays for this trial.” Indeed, while the $16.2 million trial was announced last year, and published reports had the study beginning in May or June, now researchers involved only say the trial will begin “sometime this summer.” In explaining why it is not conducting or participating in this trial, a Genentech spokeswoman said the company believes it has invented a highly successful treatment in ranibizumab, and it would rather devote its resources to explore ways of expanding the drug's use for other eye-related issues such as diabetic retinopathy. Age-related macular degeneration is the leading cause of blindness in the developed world among people aged 50 years or older. In the United States, the prevalence of people with visual loss from AMD is 1.2 million with about 200 000 new cases being reported annually. About 7.3 million people in the United States are at risk of developing the condition. The neovascular form of AMD is characterized by abnormal growth of new blood vessels involving the macula. Scientists believe that vascular endothelial growth factor (VEGF) promotes this neovascularization. Ranibizumab and bevacizumab are monoclonal antibodies that neutralize VEGF. Researchers originally considered using bevacizumab as a treatment for AMD, but it was thought that the molecule created was too big to penetrate the retina. Bevacizumab went on to become, in 2004, the first angiogenesis inhibitor approved by the FDA for treatment of colorectal cancer. In the meantime, researchers created ranibizumab by reengineering bevacizumab, resulting in a smaller molecule capable of passing through the retina. But before ranibizumab received FDA approval last year, physicians, facing patients desperate to avoid blindness, turned to bevacizumab, which they found improved vision while being well tolerated. Soon pharmacists were subdividing quantities of bevacizumab intended for colorectal cancer treatment into smaller doses for AMD. Today, anecdotal evidence suggests about half of all patients being treated for AMD receive bevacizumab. With so many patients receiving a drug off-label with anecdotally reported success, it is important to determine whether bevacizumab truly is safe and effective for AMD treatment, said Daniel Martin, MD, who will lead the National Eye Institute study. “Much of the public discussion has centered on the cost differences between Avastin and Lucentis, but the cost considerations have never been a major driver of why we're doing this study,” said Martin, who is also a professor of ophthalmology at Emory University in Atlanta. “We did this because there are tens of thousands of eyes being treated with Avastin without any clinical trial data showing efficacy and safety.” The trial will evaluate 1200 patients with new-onset untreated neovascular AMD, enrolled at 45 centers throughout the country. The patients will be randomly assigned to four treatment groups: ranibizumab once a month, bevacizumab once a month, ranibizumab as needed, and bevacizumab as needed. The “as-needed” is for patients given the drug who then are not treated again until they show signs of relapsing. “For practicing physicians, the dosing frequency question is very important,” Martin said. “Our anecdotal experience with ‘as needed’ dosing suggests that an excellent visual result can be achieved in the short term with fewer injections. However, we do not know if we are compromising the patient's long term visual outcome with this treatment strategy. Our study design should allow us to answer this question.” http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA American Medical Association

Study Aims to Clarify Efficacy, Safety of Eye Drug Treatments

Mitka, Mike
JAMA , Volume 297 (14) – Apr 11, 2007
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Publisher
American Medical Association
Copyright
Copyright © 2007 American Medical Association. All Rights Reserved.
ISSN
0098-7484
eISSN
1538-3598
DOI
10.1001/jama.297.14.1538
Publisher site
See Article on Publisher Site

Abstract

The press release seems simple enough: “The National Eye Institute of the National Institutes of Health will fund a new multicenter clinical trial to compare 2 drugs currently used to treat advanced age-related macular degeneration (AMD).” But its ramifications are enormous. The drugs in question are ranibizumab (Lucentis) and bevacizumab (Avastin), both manufactured by Genentech Inc, of South San Francisco. Currently, only ranibizumab is approved by the US Food and Drug Administration (FDA) for treating neovascular AMD. And it works well, with more than 90% of patients reporting a halt in vision loss and about 30% reporting improved sight. But a single dose of ranibizumab costs almost $2000 (or $48 000 for a typical 2-year course of monthly treatments). Although Medicare pays for ranibizumab, it covers only 80% of the cost, meaning that patients who do not have coinsurance pay $9600 out of pocket for a 2-year course. (Genentech does provide financial assistance and a free drug program for those who qualify who cannot pay for treatment.) As an alternative, a significant number of physicians are using bevacizumab off-label for AMD treatment. It costs about $40 a dose. A new multicenter clinical trial is enrolling patients with advanced age-related macular degeneration to compare the effectiveness of the only drug approved for that indication with a much less costly alternative that is being widely prescribed off-label. (Photo credit: JAMA. 2006;295:2394-2406) Payers such as Medicare and patients who lack insurance or have copays will obviously experience huge cost savings if bevacizumab is found to be as effective as ranibizumab. Such a finding would also provide another treatment option for AMD in developing countries, where ranibizumab is generally not affordable. On the flip side, Genentech stands to lose billions of anticipated dollars if ranibizumab is abandoned for AMD treatment. But beyond Genentech, the biotech and drug manufacturing industries are concerned about the precedent created by this trial and could use their political clout in an attempt to derail the study, said William Rich III, MD, medical director of health policy for the American Academy of Ophthalmology in Washington, DC. “Obviously, biotech hates head-to-head trials based on efficacy and affecting payment,” Rich said. “I’m anticipating delays for this trial.” Indeed, while the $16.2 million trial was announced last year, and published reports had the study beginning in May or June, now researchers involved only say the trial will begin “sometime this summer.” In explaining why it is not conducting or participating in this trial, a Genentech spokeswoman said the company believes it has invented a highly successful treatment in ranibizumab, and it would rather devote its resources to explore ways of expanding the drug's use for other eye-related issues such as diabetic retinopathy. Age-related macular degeneration is the leading cause of blindness in the developed world among people aged 50 years or older. In the United States, the prevalence of people with visual loss from AMD is 1.2 million with about 200 000 new cases being reported annually. About 7.3 million people in the United States are at risk of developing the condition. The neovascular form of AMD is characterized by abnormal growth of new blood vessels involving the macula. Scientists believe that vascular endothelial growth factor (VEGF) promotes this neovascularization. Ranibizumab and bevacizumab are monoclonal antibodies that neutralize VEGF. Researchers originally considered using bevacizumab as a treatment for AMD, but it was thought that the molecule created was too big to penetrate the retina. Bevacizumab went on to become, in 2004, the first angiogenesis inhibitor approved by the FDA for treatment of colorectal cancer. In the meantime, researchers created ranibizumab by reengineering bevacizumab, resulting in a smaller molecule capable of passing through the retina. But before ranibizumab received FDA approval last year, physicians, facing patients desperate to avoid blindness, turned to bevacizumab, which they found improved vision while being well tolerated. Soon pharmacists were subdividing quantities of bevacizumab intended for colorectal cancer treatment into smaller doses for AMD. Today, anecdotal evidence suggests about half of all patients being treated for AMD receive bevacizumab. With so many patients receiving a drug off-label with anecdotally reported success, it is important to determine whether bevacizumab truly is safe and effective for AMD treatment, said Daniel Martin, MD, who will lead the National Eye Institute study. “Much of the public discussion has centered on the cost differences between Avastin and Lucentis, but the cost considerations have never been a major driver of why we're doing this study,” said Martin, who is also a professor of ophthalmology at Emory University in Atlanta. “We did this because there are tens of thousands of eyes being treated with Avastin without any clinical trial data showing efficacy and safety.” The trial will evaluate 1200 patients with new-onset untreated neovascular AMD, enrolled at 45 centers throughout the country. The patients will be randomly assigned to four treatment groups: ranibizumab once a month, bevacizumab once a month, ranibizumab as needed, and bevacizumab as needed. The “as-needed” is for patients given the drug who then are not treated again until they show signs of relapsing. “For practicing physicians, the dosing frequency question is very important,” Martin said. “Our anecdotal experience with ‘as needed’ dosing suggests that an excellent visual result can be achieved in the short term with fewer injections. However, we do not know if we are compromising the patient's long term visual outcome with this treatment strategy. Our study design should allow us to answer this question.”

Journal

JAMA – American Medical Association

Published: Apr 11, 2007

Keywords: eye,bevacizumab,ranibizumab

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