Boston Scientific May Face A Tough FDA Panel

On Wednesday the FDA's Circulatory System Devices Panel will once again review Boston Scientific's Watchman left atrial appendage closure device for the prevention of stroke in atrial fibrillation patients (click here for the meeting materials). The panel will be the latest chapter in the long and contentious story of the Watchman. In 2010 the FDA issued a complete response letter and earlier this year a scandal broke out when the American College of Cardiology cancelled a prestigious late-breaking clinical trial presentation of the PREVAIL trial after the company broke an embargo by giving trial results to investors.

Wells Fargo analyst Lawrence Biegelsen predicts that the panel will be "contentious" but that ultimately the device will be approved next year. Although the trial missed one of its three c0-primary endpoints, the FDA reviewers emphasis on "the totality of the data" suggests a more benign FDA perspective, he writes.

One knowledgeable observer, Sanjay Kaul, who has served on several FDA panels, thinks the panel will indeed be contentious. He points out that PREVAIL did not meet the FDA's requirement for noninferiority to warfarin, as defined in the briefing document.

Noninferiority has to be met for both the first and second primary endpoints. Noninferiority was obviously not met for the first primary endpoint; it is debaeable if it was met for the second primary endpoint…. The third primary endpoint (safety) was BARELY met. On the basis of the PREVAIL trial, it is hard to make a case for the device. However, safety has improved.

"The problem," continues Kaul, is that the proposed indication for the Watchman is to "reduce the risk of stroke, systemic embolism, and cardiovascular death in high risk patients with non-valvular atrial fibrillation who are eligible for warfarin therapy, but, for whom the risks posed by long term warfarin therapy outweigh the benefits.” But, Kaul argues:

Since intracerebral hemorrhage is the biggest risk associated with warfarin, it is exactly in these patients that the newer oral anticoagulant agents offer the greatest advantage. So, why should we expose our patients to an invasive device that has not even been proven to be "no worse than warfarin" and that has not been shown to offer any safety (bleeding, including ICH) advantage in comparison with the new oral anticoagulants!

Even if the Watchman does get by the panel and the FDA, Kaul thinks it won't be used as first line treatment for nonvalvular AF patients: "It is hard to make a case for this device as first option treatment for NVAF."