An NIH study finds that Avastin, a drug approved to treat some cancers that is commonly used off-label to treat age-related macular degeneration (AMD), is as effective as the Food and Drug Administration-approved drug Lucentis for the treatment of AMD. The results are being reported following the first year of a two-year, multi-center study involving 1,185 patients treated at 43 clinical centers in the United States The report, from the Comparison of AMD Treatments Trials (CATT), was published online in The New England Journal of Medicine on April 28 and will be in the May 12 print edition.
Philip J. Rosenfeld, M.D., Ph.D., professor of ophthalmology and retina specialist at Bascom Palmer and author of the accompanying editorial, “Bevacizumab versus Ranibizumab — The Verdict,” pioneered the use of Avastin in the eye and his research was the impetus for the trial funded by the National Eye Institute part of the National Institutes of Health. Based on the results of his initial study in 2005 and his clinical use of Avastin in wet AMD, Rosenfeld’s colleagues from major retinal associations around the world, credit him with being the first to use Avastin as an effective treatment for AMD. The NIH then embarked on this study to compare the two drugs, head-to-head, in a large, multi-center study and determine if both treatments were the same.
More than a quarter million patients with AMD receive treatment each year and, with Avastin costing approximately $50 per treatment and Lucentis costing roughly $2,000 per treatment, the scientific results comparing the effectiveness of the two drugs has the potential to save Medicare billions of dollars. In another study led by Ross Brechner and Rosenfeld in 2008, they reported that Medicare paid for 480,000 Avastin injections to treat the wet form of AMD and 337,000 Lucentis injections. However, Medicare paid only $20 million for the Avastin compared to $537 million for 143,000 fewer Lucentis injections. “The economic ramifications for treating this disease globally are monumental,” he concluded.
“Following the findings of my earlier studies and those of my colleagues, it is reassuring to learn that both drugs are equally effective, and Avastin can serve as a low cost alternative to Lucentis,” said Rosenfeld. “This is particularly good news for the millions of patients worldwide who can avoid blindness by using Avastin as the low cost alternative.”
The neovascular or “wet” form of AMD, a degenerative condition, is the most common form of irreversible blindness and vision impairment among people 50 years of age and older in the U.S. An estimated 8 million Americans over the age of 50 suffer from AMD with 1.3 million at risk of developing wet AMD and severe vision loss. This number is expected to double by the year 2020 as baby boomers get older. In its advanced stages, the wet form of AMD spurs the growth of abnormal blood vessels, which leak fluid and blood into the macula and obscure vision. The macula is the central portion of the retina that allows us to look straight ahead and to perceive fine visual detail. Accumulation of fluid and blood damages the macula, causing loss of central vision. AMD can severely impede mobility and independence. Many patients are unable to drive, read, recognize faces or perform tasks that require hand-eye coordination.
Genentech, the maker of both drugs, originally developed Avastin to prevent blood vessel growth that enables cancerous tumors to develop and spread. In 2004, the FDA approved Avastin for the systemic (intravenous) treatment of metastatic colon cancer. Genentech later developed Lucentis, derived from a protein similar to Avastin, specifically for injection in the eye to block blood vessel growth in AMD.
In addition to Rosenfeld, numerous physicians also noted a beneficial treatment effect and Avastin’s use grew rapidly despite the lack of data typically derived from randomized clinical trials to support its use. Ophthalmologists used Avastin primarily as needed, or pro re nata (PRN), when there was evidence of active disease. The FDA approved Lucentis in 2006, however, most clinicians adopted PRN dosing for Lucentis, which was a departure from FDA-approved labeling and the monthly dosing schedule evaluated in the Genentech-sponsored clinical trials. It was not known if PRN dosing would produce the same long term vision benefits that were achieved with monthly injections.
The National Eye Institute launched CATT in 2008 to compare Lucentis and Avastin for treatment of wet AMD. Study patients were randomly assigned and treated with one of four regimens for a year. They received Lucentis monthly or PRN, or Avastin monthly or PRN. Enrollment criteria required that study participants had active disease.
In addition to the primary finding of equivalence between Lucentis and Avastin for visual acuity, CATT also demonstrates that PRN dosing is a viable treatment option for either of these drugs. “The CATT results, together with the totality of global experience, support the use of either bevacizumab (Avastin) or ranibizumab (Lucentis) for the treatment of wet AMD,” wrote Rosenfeld. “Health care providers and payers worldwide will now have to justify the cost of using ranibizumab (Lucentis). Regulators in certain countries will be forced to reconsider their policies that make it illegal to use drugs off-label particularly when so many of their citizens cannot afford ranibizumab (Lucentis),” he concluded.
Investigators in the CATT study will continue to follow patients through a second year of treatment. These additional data will provide information on longer-term effects of the drugs on vision and safety.