FDA Panel Once Again Rejects ACS Indication for Rivaroxaban

January 17th, 2014

FDA Panel Once Again Rejects ACS Indication for Rivaroxaban

Larry Husten, PHD

The FDA’s Cardiovascular and Renal Drugs Advisory Committee has once again turned down the supplemental new drug application for an acute coronary syndrome (ACS) indication for Johnson & Johnson’s Xarelto (rivaroxaban). The nearly unanimous vote (10-0, with 1 abstention) was in line with a highly negative review from FDA staff members.

Although originally the subject of high praise when it first came out, the pivotal ATLAS ACS 2-TIMI 51 trial has been bedeviled by criticism since the FDA drew attention to the unusually large amount of missing trial data. Previous discussions of the trial at the FDA brought the word “missingness” into common usage in the medical community. Although Johnson & Johnson made efforts to supply some of the missing data this time around, ultimately the panel members agreed with the most recent assessment from the FDA reviewers that the large amount of still-missing data made it impossible to reach firm conclusions about the relative safety and efficacy of the drug in the setting of ACS.

Panel member Linda Fried, from the University of Pittsburgh, gave voice to a view adopted by many of the committee members. ATLAS, she said, was probably “an overall positive study” but, because of the large amount of missing data and the absence of a confirmatory study, was “not robust enough” to support the ACS indication. Speaking on behalf of the sponsor, cardiologists C. Michael Gibson and Marvin Konstam tried to persuade the panel to accept their multiple positive analyses of the trial. But panel members, including outspoken critics like Steve Nissen and Sanjay Kaul, left little doubt throughout the day’s meeting that they were unlikely to vote in favor of the new indication.

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January 17th, 2014