Monday, April 30, 2012, Cleveland: In a landmark drug-comparison study, Cleveland Clinic researchers found that bevacizumab (Avastin) is equivalent to ranibizumab (Lucentis) in the treatment of wet age-related macular degeneration (AMD) through two years.
The study — Comparison of AMD Treatments Trials (CATT) — also showed that monthly dosing produced slightly more vision gain than as-needed dosing. But the final visual results were similar in all treatment groups, regardless of dosing frequency, with 60-percent or more of the patients achieving driving vision (20/40 vision or better).
"Both drugs were highly effective regardless of the approach to dosing," said Daniel F. Martin M.D., study chair for CATT and Chairman of the Cole Eye Institute at the Cleveland Clinic. "There was slightly less vision gain with as-needed treatment. However, patients seeking the small extra advantage of monthly treatment need to be mindful of the additional burden, risks, and costs of monthly injections. Since as-needed dosing required 10 fewer eye injections over the course of two years and yielded similar visual results, many patients may choose this option."
AMD is the leading cause of vision loss and blindness in older Americans. For many people, AMD severely impedes mobility and independence by limiting their ability to drive, read, recognize faces or perform tasks that require hand-eye coordination. Ten years ago, 60 to 70 percent of patients with wet AMD were legally blind in two years. Due to the powerful therapeutic effects of the drugs studied in CATT, only 5 percent to 10 percent of patients are legally blinded from AMD today. However, prior to the results of this trial, doctors did not know the optimal way to use these drugs or if one drug was better than the other.
"Head-to-head studies such as CATT inform the decisions that patients and physicians make every day — which drug and how often," said Dr. Martin. "CATT has proven to be an important clinical tool for patients and physicians, helping them to make informed decisions in drug choice and dosing regimen based on desired goals."
Over two years, the rates of death, myocardial infarction and stroke did not differ between drugs. In the first year of the study, there was a higher rate of non-specific serious adverse events for bevacizumab-treated patients than ranibizumab-treated patients, and this difference persisted in year two. However, the importance of this difference was unclear.
Adverse events indicate development or worsening of a medical condition. The events may or may not be causally associated with the clinical trial treatment, but they are always monitored and reported in any clinical trial. The median age of patients in CATT was over 80 years, and a high rate of hospitalizations would be anticipated as a result of chronic or acute medical conditions more common to older populations.
Serious adverse events occurred at a 40 percent rate for patients receiving bevacizumab and a 32 percent rate for patients receiving ranibizumab. Although bevacizumab had a higher rate of serious adverse events, they were distributed across many different conditions, most of which were not associated with bevacizumab when evaluated in cancer clinical trials, in which the drug was administered at 500-times the dose used for AMD. Fewer doses were associated with a higher rate of serious adverse events, which is not a typical dose-response relationship. CATT was not capable of determining whether there is an association between a particular adverse event and treatment. Additional data from other clinical trials may provide information on long-term safety profiles of these drugs when used to treat AMD.
In conjunction with the clinical findings from this study, the cost differences between treatments may have implications for both patients and physicians. One dose of ranibizumab costs approximately $2,000, while bevacizumab costs about $50 per dose. Both drugs are manufactured by Genentech.
"In 2010, ranibizumab accounted for nearly 10 percent of the entire Medicare Part B drug budget, its single largest expenditure," write the authors. "As the treatment of patients continues indefinitely, the cumulative financial burden to third-party payors and patients will only increase."
Funded by the National Eye Institute, as part of the National Institutes of Health, CATT sought to compare the relative safety and effectiveness of the two drugs in treating wet AMD. Ophthalmologists began using bevacizumab while awaiting FDA approval of ranibizumab, because of the drugs' structural similarities. Bevacizumab, approved by the FDA for treating colorectal cancer, has been widely prescribed off-label by ophthalmologists to treat AMD since 2005.
"Results of this clinical trial provide evidence that long-term treatment with either drug results in a robust and lasting improvement in vision," said Paul A. Sieving, M.D., Ph.D., director of the NEI. "Patients and clinicians now have valuable information to base treatment decisions."