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Genentech letter: Increased stroke risk with 0.5-mg dose in Lucentis SAILOR study
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Genentech issued a letter to physicians last week informing them of an increased incidence of stroke in patients receiving 0.5 mg intravitreal injections of ranibizumab in a clinical trial. Patients with a history of stroke appeared to be at higher risk for subsequent strokes, the letter said.
The higher incidence of stroke was identified during a planned interim safety analysis in the SAILOR (Safety assessment of intravitreal Lucentis for age-related macular degeneration) trial. Patients had been receiving Lucentis (ranibizumab, Genentech/Novartis) for an average of 230 days before the analysis was performed.
Investigators found a 1.2% incidence of stroke in patients receiving a 0.5 mg dose of ranibizumab compared with a 0.3% incidence in patients receiving a 0.3 mg dose (P = .02), according to the letter sent to physicians by Genentech. The marketed version of Lucentis is a 0.5 mg dose.
The incidences of myocardial infarction and vascular death were not statistically significantly different between the doses, according to the letter.
The SAILOR trial is a phase 3b study initiated in November 2005 that includes about 5,000 patients at more than 100 sites in the United States. The study is comparing the safety of 0.5 mg and 0.3 mg doses of ranibizumab in a sub-cohort of 2,400 patients.
"Because of how many patients are in that study, we're able to potentially detect rare events with statistical significance that we would not be able to pick up in smaller studies," said Genentech spokeswoman Dawn Kalmar in a telephone interview with Ocular Surgery News. The company's two pivotal trials of Lucentis, ANCHOR and MARINA, included 423 and 716 patients, respectively.
"[The rates] are consistent with what we've seen in the past. The difference now is that there is statistical significance due in part to the size of the study," Ms. Kalmar said.
Genentech issued the letter as a "proactive effort," Ms. Kalmar said, and not as a result of a mandate from the Food and Drug Administration.
She noted that the FDA has been made aware of the data and has requested follow-up. The company indicated in the letter that it intends to review safety data upon completion of the SAILOR study in late 2007.
Company officials do not anticipate a change to Lucentis' label, Ms. Kalmar noted.
"[The label] includes a theoretical risk of arterial thromboembolic events including stroke, ... and they qualify as low, as [they were] less than 4%. So these rates of 1.2% fall within that," she said.
The letter directs physicians with questions to call the Medical Information/Communications Department of Genentech, at 800-821-8590.