On February 22, 2008 the National Eye Institute (NEI) of the National Institutes of Health (NIH) announced the start of a multicenter clinical trial ("Comparisons of Age-Related Macular Degeneration Treatments Trials") to study the relative safety and effectiveness of Lucentis (ranibizumab) and Avastin (bevacizumab). Both anti-angiogenic drugs are being used for treatment of wet AMD.
According to Paul A. Sieving, M.D., Ph.D., director of NEI, the 2-year CATT study "will evaluate whether the treatment burden for patients can be reduced without compromising effectiveness."
The trial will involve 1,200 patients, who will be treated with injections of either Lucentis or Avastin on a fixed schedule of once every four weeks for one year. In the second year, the patient will be assigned randomly to either an injection of the same drug every four weeks or on a variable schedule depending upon response to treatment.
The primary outcome measure will be change in visual acuity. Secondary outcome measures will include number of treatments, anatomical changes in the retina, adverse events, and cost.
The trial will be conducted at 47 clinical centers across the country. For a list of centers, eligibility recruitments, and other information, see http://www.nei.nih.gov/CATT.
BACKGROUND
The following information is provided for review of the purpose and history of the two drugs under study.
Wet AMD occurs when abnormal blood vessels behind the retina start to grow under the macula. These new blood vessels leak blood and fluid, damaging the macula and causing a rapid loss of vision. The growth of new blood vessels is called angiogenesis or neovascularization. A protein called vascular endothelial growth factor (VEGF) has been found to be an important element in angiogenesis. This discovery provided a stimulus for the development of a number of anti-angiogenic (anti-VEGF) drugs, which can be read about in the MD Support Library . Two of these drugs, Lucentis and Avastin, are manufactured by Genentech, a large pharmaceutical company located in South San Francisco.
Lucentis was approved by the U.S. Food and Drug Administration (FDA) in June 2006 for the treatment of advanced, or wet, AMD. The approval was based on clinical trials showing that Lucentis slowed the rate of progression of vision loss from wet AMD in up to 94% patients. In addition, approximately one-third of patients treated in these trials showed improved vision after treatment.
Avastin is a similar drug approved by the FDA in 2004 as an intravenous treatment for patients with advanced colorectal cancer. Due mainly to its lower cost than Lucentis, it has been widely used off-label to treat wet AMD. Also, Avastin (due to the larger molecule) remains in the eye longer than Lucentis, possibly allowing for less frequent injections. According to Genentech, however, this longer half-life may allow it time to negatively affect other parts of the body. This and other safety factors are expected to be clarified by the NEI trials.