FDA Continues Probe of Califf’s Xarelto ROCKET Trial
FDA says it is continuing to review relevant data about an allegedly faulty device that was used in a clinical trial supporting approval of Bayer’s Xarelto (rivaroxaban). The blood thinner, marketed in the U.S. by Johnson & Johnson’s Janssen unit, is indicated to prevent ischemic stroke in non-valvular atrial fibrillation. The trial was supervised by FDA commissioner-nominee Robert Califf while he was at Duke University.
Doctors and scientists reportedly are saying that there should be an independent investigation into the Duke Clinical Research Institute ROCKET-AF trial because its results could have been compromised through use of a recalled point-of-care device to measure international normalized ratio (INR) in trial patients taking warfarin (see earlier story). Faulty INRatio device readings could have led to patients receiving higher warfarin doses than needed, with a greater risk of bleeding.
While FDA is reviewing the issue, an agency spokeswoman told FDA Webview 2/23 that Califf is recused from the matter. “This class of drug has proven safe and effective in trials and in post-marketing assessments, as noted by Dr. Ellis Unger, of the Office of New Drugs at the FDA, in a recent post on FDA’s Web site,” she said.
“At FDA,” the spokeswoman continued, “we are constantly examining patient safety data and conducting other surveillance activities after products are on the market to ensure that the labels reflect current knowledge with regard to benefits and risks. These data are quite valuable for understanding possible side effects and for assessing whether reported concerns are caused by the drug. We continue to actively monitor the safety of Xarelto. FDA has not changed its recommendations regarding the use of Xarelto; it provides an important health benefit when used as directed.”
FDA has asked Johnson & Johnson detailed questions about whether there was evidence the device was malfunctioning during the trial, according to a legal brief reviewed by the New York Times that was filed in federal court by lawyers for patients and their families who say they were injured by the drug. The lawyers also cited internal company documents that they said showed doctors were complaining to the trial leadership during the course of the study.
Criticisms about the trial have dogged Califf as his nomination has moved through the Senate. At the end of 2015, the Project on Government Oversight (POGO) said that Califf “helped lead a clinical trial that was sharply criticized by FDA reviewers and some outside advisors to the agency.” POGO said that as commissioner, Califf would “hold considerable sway over decisions that affect the interests of the drug industry and the health and safety of the public. Dr. Califf’s handling of the Xarelto trial raises concerns about his judgment in overseeing the pharmaceutical industry.”