Xarelto Receives FDA Priority Review – But, is it Really a Major Advancement?

When a new drug is introduced and the manufacturer claims that the drug is supposed to either offer a major advancement in treatment or provide a treatment where no adequate treatment exists, the U.S. Food and Drug Administration gives the drug “priority review” status, meaning more FDA resources will be directed towards reviewing the drug than would be typical, with the goal of completing review of the drug in six months rather than the ten to twelve months the FDA usually spends reviewing standard drugs.

Xarelto, like its competitor Pradaxa, has been in a race to grab the potentially lucrative $10 billion market to replace the generic blood thinner, warfarin, which is used in treatment of atrial fibrillation – a rapid, irregular heart rhythm. Boehringer Ingelheim’s blockbuster drug, Pradaxa, got a leg up on the market when it was approved in 2010. Xeralto, licensed by Janssen Pharmaceuticals from Bayer, followed closely by receiving FDA approval in 2011. Eliquis, an effort from Pfizer and BMS, is the third drug in the new-generation blood thinner market, but has fallen behind with word from the FDA that more information would be needed before it could be approved.

Janssen now looks to expand the Xeralto market with additional indications for use in treatment of deep vein thrombosis (DVT) and pulmonary embolism. But is Xarelto really a major advancement in the treatment of DVT?

The treatment of DVT requires an anticoagulant to prevent a blood clot from getting bigger. Two different types of anticoagulants have been used to treat DVT for years – heparin and warfarin. Heparin is generally prescribed first, because it works immediately to prevent further clotting. After the initial heparin treatment, warfarin may also be prescribed to prevent another blood clot from forming.

Manufacturers of new drugs, such as Xarelto and Pradaxa, seek to capture the warfarin market for DVT treatment. Although the manufacturers point to improvements over warfarin, warfarin still has one major advantage that can’t be ignored – the blood thinning action of warfarin can be quickly reversed in patients who suffer bleeds by administering vitamin K. On the other hand, each of the three of the new-generation blood thinners lacks a way to reverse the drug’s intended action, leading some top cardiologists to say that they are not ready to prescribe any of the new thinners.

The lack of a reversal agent is part of the reason lawsuits have been brought against Pradaxa’s manufacturer Boehringer Ingelheim since Pradaxa hit the market in 2010. Many people are worried that Xarelto may be following the same path. According to the Adverse Events Monitor, a report that tracks the FDA’s Adverse Event Reporting System, Xarelto was the subject of 990 primary suspect reports in the first two quarters of 2012, with the top reported adverse event being pulmonary embolism.

Given the extent of adverse events associated with Xarelto, the FDA’s allocation of additional resources to investigate the drug prior to approving it for additional uses is warranted. It seems far from certain that Xarelto is really a major advancement from warfarin, and because it lacks a reversal agent, presents risks similar to those that have resulted in litigation over Boehringer Ingelheim’s Pradaxa.