New-generation anticoagulants may be a tougher sell than drugmakers first thought. When warfarin alternatives were first nearing the market, expectations were quite high. Notoriously difficult to dose and manage, warfarin seemed ripe for the overtaking, and the market for new choices was estimated at $10 billion-plus. But as Reuters reports, doctors aren't as enthusiastic as market-watchers have been.
The problem lies in one key difference between warfarin and this new group of rivals: Warfarin's effects can be quickly reversed with an antidote. That's not true of the new drugs--including Pradaxa, from Boehringer Ingelheim; Xarelto, from Bayer and Johnson & Johnson ($JNJ); and the waiting-in-the-wings Eliquis, from Bristol-Myers Squibb ($BMY) and Pfizer ($PFE).
Though the new drugs don't require constant monitoring like warfarin does, there are bleeding risks, common with anti-clotting medications. But Pradaxa, for instance, can interact with other drugs, affecting its performance. Patients with poor kidney function are at particular risk of bleeding, because concentrations tend to build up in their bloodstreams.
More than 500 deaths in Pradaxa patients were reported to FDA last year, compared with 72 for warfarin, Reuters notes, though at least one FDA official believes that warfarin issues may go unreported because of its known risks after years of use. (Some 2.2 million Pradaxa scripts were written in the U.S. last year.) Though similar stats haven't been reported on Xarelto--it's been on the U.S. market only since last July, with its biggest indication approved in November--more than a dozen doctors told Reuters they have similar concerns about the Bayer-J&J drug.
Lawsuits against Boehringer are piling up. European regulators asked the company to add warnings about Pradaxa's bleeding risks to its labeling there. FDA put the drug under a safety review in December, but affirmed its risk-benefits balance at the time. FDA's Dr. Robert Temple said the agency is keeping an eye on the adverse event report numbers, skewed as they are toward Pradaxa. "We don't necessarily believe it is real," he said. "But we're watching it. We can't help but notice it."
The companies maintain that evidence of the most serious bleeding events was greater with warfarin in clinical trials comparing the old drug with the new ones. If doctors use the drugs properly--including testing kidney function before use--problems can be avoided, cardiologist Dr. Sanjay Kaul told the news service. "I have received a dozen phone calls form local colleagues in the last couple of months about bleeding on Pradaxa and have yet to find a single case where that bleeding was not related to improper use of the drug," he said.
- see the Reuters analysis