FDA Advisory Panel Backs Xarelto to Prevent Strokes
Panel Members Recommend Approval of New Blood Thinner for Patients With Atrial Fibrillation
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Questions About Study Design
The panel's discussion centered on the findings of the company-sponsored ROCKET-AF study. The results of that study were published last month in The New England Journal of Medicine.
Panel members say they were particularly concerned that many of the patients in the study who were taking warfarin didn't seem to have been getting optimal doses of that drug.
As a result, FDA reviewers said, Xarelto may have looked more effective in the study than it actually was.
Nearly 40% of the 14,000 patients in the trial were in countries in Eastern Europe, where doctors had the most trouble managing patients on warfarin.
"The ROCKET study enrolled the majority of their patients in countries that don't use warfarin well," says Martin Rose, MD, JD, who reviewed the clinical data on Xarelto for the FDA, in his presentation to the panel.
Rose also points out that among six other recent trials of blood-thinning drugs, ROCKET-AF had the fewest number of patients on warfarin who were maintained at an optimal dosage that would prevent strokes.
Other trials had kept as many as 68% of patients on an optimal warfarin dose. Only 55% of patients in the ROCKET trial were kept within a so-called optimal therapeutic range.
Other concerns cited by the panel included a high rate of adverse events in patients soon after they discontinued Xarelto, an issue they said warranted further study.
Investigators who led the ROCKET trial defended the quality of the study.
"We gave warfarin not only in an acceptable way, we gave it in a commendable way during this trial considering the complexity of the trial design that we had," says Robert M. Califf, MD, vice chancellor of clinical research at Duke University.
Califf points out that warfarin is known to be a drug that's difficult for doctors and patients to use.
Warfarin works by blocking vitamin K, so foods that are high in that nutrient, like dark leafy green vegetables, can interfere with its effect. Many medications also interact with the drug.
Patients enrolled in the trial, Califf pointed out, had many other medical conditions and were taking an average of nine other medications in addition to their blood thinner.