FDA stalls the blood-thinner Xarelto’s approval citing inadequate evidence

By Dr. Ananya Mandal, MDSep 6 2011

The Food and Drug Administration (FDA) said in a staff report released today that “there is insufficient information about the drug to determine whether it is safe for use with its proposed labeling.” Their report questions its safety and effectiveness, saying a new study is needed.

Xarelto - chemically known as rivaroxaban, is one of several promising drugs used to replace warfarin for people with dangerously irregular heart rhythms, called atrial fibrillation (AF). Individuals who take warfarin have irregular heartbeats that can cause blood to pool, increasing their risk of clots and strokes. Unfortunately, taking warfarin requires regular blood tests. Currently, Xarelto is used to reduce the risk of blood clots, deep vein thrombosis, and pulmonary embolism following knee or hip replacement surgery.

This review represents a blow to the drug companies, especially when analysts expected Xarelto to generate more than $1 billion in sales revenue. Johnson & Johnson, which developed the anti-clotting drug with Bayer Healthcare, says it has lots of evidence Xarelto is effective.

Additionally, the FDA review was good news to Xarelto’s rival treatment called Eliquis. Eliquis is being developed by Bristol-Myers Squibb and Pfizer Inc as an anti-clotting drug that could peak at $10 billion per year. Eliquis, also known as apixaban, showed superiority over warfarin in effectiveness, safety and saving lives in a clinical trial. These results were presented last month at a scientific meeting in Paris, and reaffirm its place as top competitor.

The FDA report included a disclaimer that the conclusions of the reports are not their final position of the reviewers or the entire agency. Outside experts will be reviewing the data and host a discussion, with a decision announcement on Thursday. This Thursday decision is not binding and after the public decision, the FDA will make a decision, privately.

Xarelto had a 31 percent lower risk of major bleeding, a safety concern with blood thinners, compared with warfarin and an 11 percent reduced risk of dying, the first time a warfarin replacement has saved lives in a clinical trial.

In a study of 14,264 patients, 188 patients taking Xarelto suffered a stroke or artery obstruction compared with 241 taking warfarin, according to results published in the New England Journal of Medicine. Rates of major bleeding were similar in the Xarelto and warfarin groups. Slightly more patients on Xarelto experienced non-major bleeding, 1,475 compared with 1,449 on warfarin.

The comparison group of patients given warfarin during the study was in the recommended treatment range just 55 percent of the time. In separate studies of Xarelto’s rivals, the comparison groups on warfarin did better, with patients remaining in the therapeutic window 64 percent of the time during the Pradaxa trial and 62 percent in the apixaban trial. The study said Xarelto was tested on higher-risk patients. Pradaxa and apixaban are given twice daily while Xarelto is taken once a day.