The safety message on Boehringer Ingelheim's key product, Pradaxa, has been mixed. But the German drugmaker, which is going through a tough financial period, has rolled out some new studies at the American Heart Association's Scientific Sessions that show its effectiveness, as well as some promising data about the antidote being developed to treat serious bleeding in Pradaxa patients.
"New data on the investigational antidote idarucizumab show that it can reverse the effect of the oral anticoagulant Pradaxa (dabigatran etexilate) on both blood coagulation and the blood clotting mechanism," the drugmaker reported of results from a Phase I study on 35 healthy volunteers. "This is the first time that an antidote to a novel oral anticoagulant (NOAC) has demonstrated such an effect."
The new anticoagulants, like Pradaxa, Xarelto from Bayer and Johnson & Johnson ($JNJ), and Pfizer ($PFE) and Bristol-Myers Squibb's ($BMY) Eliquis, have become popular because they are much easier to administer than warfarin, the drug they replace. But the risk of serious, sometimes fatal, bleeding is boosted by their blood-thinning effects. Warfarin has an antidote that can stanch the bleeding, but the new meds do not, and so the companies are all supporting work to develop one. Last month, a Phase III study showed that Portola Pharma's ($PTLA) FDA-designated breakthrough candidate met both its primary and secondary endpoints with high statistical significance, immediately reversing Eliquis' effects.
The other studies Boehringer announced today showed a reduced risk of major bleeding and reduced incidence of major stroke compared to warfarin. A study by Brigham and Women's Hospital using U.S. health insurance data reported a 25% reduction in bleeding and a numerical 23% reduction in stroke, the company said. The second study from Walter Reed National Military Medical Center using data from the U.S. military health system demonstrated a 13% reduction in bleeding and 27% fewer strokes. Results also showed 35% fewer myocardial infarctions and a 36% improvement in survival compared to warfarin. The risk for gastrointestinal bleeding, on the other hand, was 30% higher, a finding that was consistent with some other studies.
The new results come on top of another study that Boehringer pointed to earlier this month. That study, overseen by the FDA and published in Circulation, showed no difference in bleeding risk between Pradaxa and warfarin. That study examined records on 134,000 Medicare patients with atrial fibrillation.
But on the same day, a study published in JAMA Internal Medicine reported very different conclusions from a study that was smaller but was said to better factor in differences between patients taking the two drugs than the FDA study. Its conclusion? Pradaxa patients had a 30% greater risk of any bleeding, 58% greater risk of major bleeding and 85% higher risk of gastrointestinal bleeding. It also found that the risk of bleeding in the brain was reduced in patients on Pradaxa compared to those on warfarin, a factor the authors concluded makes the drug useful.
The questions over Pradaxa's safety have led to thousands of lawsuits against Boehringer Ingelheim. Earlier this year it agreed to fork over $650 million to settle 4,000 lawsuits alleging that the blood thinner caused serious bleeding. It cited the settlement as one of the drags on its earnings when it reported that its revenues in the first half of the year were off 3%. Its drug sales were down 5.4% to €4.8 billion ($6.4 billion). Boehringer gets about a third of its drug sales from one drug, its COPD treatment Spiriva, but Pradaxa is also important. Last year saw sales of the anticoagulant grow 9% to €1.2 billion. The drugmaker has taken steps to counter its flagging revenues, cutting jobs to save money. In September, it said it would hack 650 jobs to achieve about $580 million in annual cost cuts.
- here's the announcement on safety and effectiveness
- read the release on the antidote candidate
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