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Posted by on Dec 28, 2010 in Cardiology, FDA, Neurology, Pharma

Top 10 for ’10: No. 4

Top 10 for ’10: No. 4

Pradaxa.jpg

No. 4: PradaxaDrum Major for the Coming Anticoagulant Parade

In October, the FDA approved dabigatran (trade name, Pradaxa), the first drug to seriously challenge and potentially replace warfarin in the anticoagulant market. The direct thrombin inhibitordeveloped by the private, German company Boehringer Ingelheimis a potential uber-blockbuster, because it is a potential godsend for those patients with atrial fibrillation who would otherwise require warfarin to reduce the risk of stroke. Pradaxa’s main advantage over the traditional anticoagulant: It does not necessitate laboratory monitoring (ie, protime measurements) and the consequent (and constant) adjustments of dosage.

On the basis of the huge RE-LY trial, the FDA approved Pradaxa at a dosage of 150 mg BID, which (when compared with warfarin) provided superior efficacy and comparable safety. An alternate dosage in the trial, 110 mg BID, wascuriously enoughnot approved by the FDA, despite the fact that it showed comparable benefits to warfarin. Instead the agency gave a nod to a 75-mg alternative for renally compromised patients, on the basis of pharmacokinetic studies.

It’s a regulatory decision that leaves many clinicians, save for cardiologist Sanjay Kaul, scratching their heads. In October, Kaul told told heartwire, “The 110-mg dose, while associated with reduced bleeding, had a 12% higher incidence of ischemic stroke. In my opinion, it would not offer much of an advantage over warfarin and would likely be an ineffective alternative.”

But not allowing the 110-mg pill on the US market leaves Americans who don’t respond reliably to warfarin and who can’t tolerate the 150-mg BID dosage of Pradaxa with no reasonable options. In an effort to cater to these patients, some US physicians have been attempting to approximate the 110-mg BID dosage of Pradaxa by prescribing 75 mg TID; however, finding adequate pharmacy stocks of the 75-mg pill has been difficult, according to anecdotal reports. For some patients, this means returning to warfarin therapy and all its attendant frustrationsfor the time being.

Pradaxa’s FDA approval was followed, 1 month later, by the publication of a favorable, independent cost-effectiveness studywhich showed that BI could justify asking up to $13.70 per day for its 150-mg BID regimen. But the company, in a show of fiscal responsibility, set a wholesale acquisition price at $6.75 per day, or $202.50 per month. The website destinationrx.com offers 60, 150-mg pills for $218.70.

The advent of Pradaxa may signify something more than just 1 option for warfarin-requiring patients. It may herald a Pharma resurgence, according to Forbes’s Matthew Herper (The Medicine Show). Herper predicts that several emerging anticoagulants, along with Pradaxa, will likely replace warfarin altogether. Among these is Bayer Healthcare’s Xaralto (rivaroxaban), a direct factor Xa inhibitor, which may be as good as or better than warfarin for preventing stroke in a-fib patients, according to clinical data presented in November at the American Heart Association meeting. Other promising, warfarin-shunning candidates in development include edoxaban (Daiichi Sankyo) and betrixiban (Merck).

However, one potential competitor, BMS/Pfizer’s apixaban, recently hit a development brick wall. Excess bleeding in the APPRAISE-2 trial, a large phase 3 study of the factor Xa inhibitor (like Xarelto), led to a screeching halt of the trial. According to a joint company press release, “There was clear evidence of a clinically important increase in bleeding among patients randomized to apixaban. This increase in bleeding was not offset by clinically meaningful reductions in ischemic events.”

But the APPRAISE-2 trial was just 1 of 9 trials assessing the potential benefits of apixaban in patients at risk of ischemic events. Other conditions in which apixaban continues to be investigated are a-fib and venous thromboembolism.

APPRAISE-2 = Apixaban for Prevention of Acute Ischemic Events-2; RE-LY = Randomized Evaluation of Long-term Anticoagulant Therapy.

* And despite the fact that it is approved in Europe and Canada.

bmartin (1130 Posts)

A native East Tennessean, Barbara Martin is a formerly practicing, board-certified neurologist who received her BS (psychology, summa cum laude) and MD from Duke University before completing her postgraduate training (internship, residency, fellowship) at the Hospital of the University of Pennsylvania in Philadelphia. She has worked in academia, private practice, medical publishing, drug market research, and continuing medical education (CME). For the last 3 years, she has worked in a freelance capacity as a medical writer, analyst, and consultant. Follow Dr. Barbara Martin on and Twitter.