Xarelto Antidote to Reverse Bleeding Problems May Have Been Found by Portola

Portola Pharmaceuticals indicates that it has developed an antidote for Xarelto, which could be used to help reverse the blood thinning effects of the blockbuster drug and reduce the risk of uncontrollable bleeding problems that have caused many users to suffer severe and often fatal injuries.

In a press release issued January 9, the drug maker claims that a clinical trial shows that a drug called andexanet alfa may be an effective Xarelto reversal agent.

“Results showed that the study met its primary endpoint with high statistical significance,” according to Portola. “Andexanet alfa administered as an intravenous (IV) bolus significantly and immediately reversed the steady-state anticoagulation activity of XARELTO and was well tolerated.”

Xarelto (rivaroxoaban) is a new-generation anticoagulant introduced jointly by Bayer and Johnson & Johnson’s Janssen subsidiary in 2011, as an alternative to Coumadin (warfarin), which has been the go-to treatment for prevention of blood clots for years. However, unlike warfarin, which can be quickly reversed if bleeding problems develop, Xarelto was introduced without an approved and effective antidote.

Portola indicates that it plans to release the full data on the potential Xarelto antidote at the American College of Cardiology’s 64th Annual Scientific Session in March.

The announcement comes as Bayer and Johnson & Johnson continue to face a growing number of Xarelto lawsuits filed on behalf of individuals who have suffered severe bleeding problems that doctors were unable to stop, alleging that the drug makers should have developed an antidote before introducing the medication. Plaintiffs also allege that inadequate warnings were provided for consumers about the potential Xarelto bleeding risks.

Xarelto is one of several new blood thinners introduced in recent years as a superior alternative to warfarin. Known as Factor Xa inhibitors, other members of this new-generation of drugs includes the widely marketed Pradaxa, which is manufactured by Boehringer Ingelheim, and Eliquis, which is sold by Bristol-Myers Squibb and Pfizer. The FDA also recently announced the approval of a fourth member of this class, Savaysa (edoxaban), which will be marketed by Daiichi Sankyo.

None of these new competitors to warfarin have approved reversal agents, and all of the manufacturers have been racing to be the first to obtain a successful antidote, hoping to gain a market advantage.

Bleeding Lawsuits Preceded Rush To Develop Blood Thinner Antidotes

As the popularity of the new generation of drugs has increased, concerns have emerged about the bleeding risk of Xarelto and Pradaxa, as large numbers of adverse event reports have been linked to uncontrollable bleeds among users of the medications.

Pradaxa (dabigatran) was introduced by Boehringer Ingelheim in October 2010, as the first member of this new generation of anticoagulants. Xarelto (rivaroxoaban) was introduced in 2011, as the second member of this class, and it has since grown to become the best seller of the two.

Boehringer Ingelheim has previously faced over 4,000 Pradaxa lawsuits alleging that the drug maker provided inadequate warnings for consumers and the medical community. Following several years of litigation, a Pradaxa settlement agreement was announced earlier this year, with Boehringer Ingelheim agreeing to pay $650 million to resolve the claims for an average of about $150,000 each.

Bayer and Janssen now face a growing number of lawsuits over Xarelto, which raise similar allegations that the drug makers placed their desire for profits before the safety of consumers by aggressively marekting the drug without adequate warnings, and for failing to fully explore all potential reversal agents that may have made the medication safer. Many plaintiffs also allege that the benefits provided by the medication do not justify the risks, indicating that the drug makers should issue a Xarelto recall until a reversal agent can be developed.

Since the Pradaxa settlement, there has been a strong competition between the companies to develop reversal agents, with most of those efforts being led by Portola. The company has also reported success in clinical trials for an antidote for Eliquis.

In June, the FDA granted Breakthrough Therapy Designation to the drug idarucizumab, being developed by a reversal agent for Pradaxa. In November, Boehringer Ingelheim, which is developing the drug, issued a press release claiming that idarucizumab can reverse the effects of Pradaxa.

The FDA breakthrough status puts the drug’s development on a fast track, as many observers indicate that the new blood thinner which releases a reversal agent first may claim a significant increase in its market share among blood thinners used to prevent strokes in patients with atrial fibrillation.