Approval of New Blood Thinner May Require Restrictions on Use

Federal drug regulators are considering approval of a new blood thinner by Daiichi Sankyo, but some indications suggest that the drug may only be good for those who suffer significant kidney problems, as it appears to work worse than existing drugs among individuals whose kidneys are healthy. 

The FDA’s Cardiovascular and Renal Drugs Advisory Committee is scheduled to meet today to discuss whether to recommend that the FDA approve the blood thinner Savaysa (edoxaban), a Factor Xa inhibitor that is similar to other new-generation blood thinners like Xarelto, Pradaxa and Eliquis.

In briefing materials (PDF) provided ahead of the meeting, FDA reviewers warn that it looks like the drug may only work better to treat patients with atrial fibrillation when given to those with bad kidneys. The review compared the proposed drug to warfarin; the go-to atrial fibrillation blood thinner that has been on the market since the 1950s.

According to the review, Savaysa, the proposed brand name of the new blood thinner, only outperforms warfarin in patients with poor renal function.

Kidney function is an important metric in the use of blood thinners because the healthier the kidneys are, the better they are at filtering out the blood thinning drug, meaning that there will be less of a chance for dangerous bleeding events. In many cases, patients need to have the levels of blood thinners monitored through regular testing.

The reviewers note that they see little need for the drug since it does not appear to outperform Xarelto, Pradaxa and Eliquis, which are all part of a new-class of anticoagulants designed to be easier to take than warfarin, since the manufacturers claim that patients do not require regular blood monitoring. However, the new generation of blood thinners have been linked to concerns about uncontrollable bleeding problems, since they lack a safe and effective reversal agent like warfarin has, which doctors can use to stop the blood thinning effects of the drug.

“Edoxaban has no proven advantages over any of the 3 direct-acting anticoagulants approved for stroke prevention in patients with atrial fibrillation,” the reviewers wrote.

While the advisory committee’s recommendations to the FDA are not binding, the agency usually weighs those recommendations considerably when making final decisions.

Bleeding Concerns with Xarelto, Pradaxa, Other New Blood Thinners

The anticoagulant warfarin, which is sold under the brand name Coumadin, has been the go-to blood thinner for prevention of stroke among individuals with atrial fibrillation for decades.

In recent years, factor xa inhibitors like Pradaxa, Xarelto and Eliquis have been introduced by drug makers attempting to capture the lucrative anticoagulant market. However, serious concerns have emerged about the safety of the drugs, and it is unclear whether the bleeding risk with this latest proposed member of the class will be considered by the panel in determining whether to provide approval for Savaysa.

While all anticoagulants carry a risk of bleeds, doctors are able to quickly reverse the blood thinning effects of warfarin with a dose of vitamin K-based prothormbin complex concentrates (PCCs) and fresh frozen plasma (FFP), which acts as an antidote to reverse the medication if bleeding problems develop. However, no such reversal agent is available for Xarelto and other members of this new class, leading to a number of reports involving serious injury or death associated with uncontrollable bleeding.

Pradaxa was the first member of this new generation of drugs to be approved by the FDA in late 2010. However, shortly after it was introduced by the drug maker Boehringer Ingelheim, it quickly earned the dubious distinction as one of the most commonly cited medications in adverse event reports submitted to the FDA, often involving problems with uncontrollable hemorrhages and death.

Boehringer Ingelheim subsequently faced more than 9,000 Pradaxa lawsuits filed on behalf of individuals who alleged that the drug makers failed to adequately warn about the lack of a reversal agent. Earlier this year, the drug maker agreed to pay $650 million in Pradaxa settlements to resolve the litigation, averaging about $150,000 per case.

Amid concerns about the safety of Pradaxa, the second member of this class, Xarelto, increased in popularity. However, reports of bleeding complications with Xarelto have also begun to emerge, leading to a number of similar Xarelto lawsuits being filed against Bayer Healthcare and Johnson & Johnson’s Janssen subsidiary.

Many of the complaints allege that the drug makers should issue a Xarelto recall until a reversal agent can be developed, arguing that the bleeding risks outweigh any benefits provided over warfarin, which has been the go-to anticoagulation treatment for decades.

All of the manufacturers of factor xa inhibitors are currently working to identify and obtain approval for an effective reversal agent, which may help increase popularity of their medication and reduce the risk of bleeding injuries and deaths.

Boehringer Ingelheim recently announced that the FDA has granted “breakthrough status” to fast-track the approval process for a possible antidote to the blood thinner Pradaxa, and Bayer and Johnson & Johnson indicated last year that they are working with a company called Portola Pharmaceuticals to develop an Xarelto reversal agent.