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Wait for 1-year SAILOR results before making conclusions on stroke risk, surgeon says
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DANA POINT, Calif. — Physicians should wait for the 1-year results of a study comparing two doses of ranibizumab before drawing any conclusions about the drug's safety, particularly regarding the risk of stroke, according to Philip J. Rosenfeld, MD, PhD.
Dr. Rosenfeld delivered the Millennium Lecture here at the Ocular Drug and Surgical Therapy Update meeting. He said it was too early to make definitive conclusions based on current data from the SAILOR (Safety assessment of intravitreal Lucentis for age-related macular degeneration) trial, a phase 3b study involving about 5,000 patients.
An interim analysis of SAILOR data completed earlier this year showed an increased incidence of stroke in patients receiving a 0.5 mg dose of ranibizumab (Lucentis, Genentech). This led Genentech in January to issue a letter to physicians informing them of the increased stroke incidence.
At the time, Ocular Surgery News reported that investigators found a 1.2% incidence of stroke in patients receiving the marketed dosage of the drug.
"One possible explanation for this phenomenon is that it [was] an interim analysis [and] that is unreliable. The stroke rate we saw was actually below the expected rate," Dr. Rosenfeld said. "None of these studies, designed for [U.S. Food and Drug Administration] approval, are powered to pick up small differences in adverse events."
Another possibility is that the phenomenon is real, but past studies have been too small to detect it, he added.
"Lucentis therapy improves vision [and] right now it has an acceptable safety profile, but we are going to pay attention to the SAILOR results, and you may only need to use it five or six times a year," he said.
Dr. Rosenfeld has been at the forefront of the development of anti-VEGF therapies for treating exudative age-related macular degeneration and has studied both Lucentis and Avastin (bevacizumab, Genentech) for wet AMD.
"To this day I still think systemic Avastin is probably the most effective treatment for this disease," Dr. Rosenfeld said, noting that patients at Bascom Palmer Eye Institute in Miami received 7,200 injections of intraocular Avastin in 2006 alone.
Avastin received FDA approval for treating metastatic colorectal cancer in 2004 but has been studied off-label to treat wet AMD. The potential risks of systemic treatment forced Dr. Rosenfeld and colleagues to find alternative ways of delivering the drug.
"We cut the dose in half and got the same efficacy, but there was still a potential risk," he said.
In May 2005, Dr. Rosenfeld asked the pharmacist at Bascom Palmer to divide one dose of systemic Avastin into individual syringes each containing about 1 mg of the drug — about a 400 times lower concentration.
"Our feeling was with less drug we had even lower systemic risk, and the cost was really cheap," he said. "Right now the current thinking is that Avastin is the first-line [treatment] for patients who cannot afford Lucentis."