Preliminary materials from the FDA on the Watchman anti-stroke device from Boston Scientific (NYSE:BSX) show that the agency has its doubts about whether to allow the cardiac implant onto the U.S. market.
The FDA’s Circulatory Devices advisory panel is slated to meet Oct. 8 for an unprecedented 3rd review of clinical trial data for the Watchman device. Despite an initial vote recommending approval, the FDA denied in March 2010 issued a "not approvable" letter to Marlborough, Mass.-based Boston Scientific.
A 2nd panel voted 13-1 last year that the Watchman implant meets safety and efficacy goals. The device is designed to reduce the risk of stroke by closing off the heart’s left atrial appendage. Boston Scientific launched the Prevail trial to address safety concerns raised by a previous Watchman trial, Protect AF, which showed that treatment with the Watchman device reduced a patient’s risk of hemorrhagic stroke compared with warfarin, but also showed an increase in procedure-related adverse events.
That data, submitted in June, prompted the agency to schedule the 3rd advisory panel meeting. Preliminary meeting materials released today show that the FDA isn’t sure about the data from the 2 trials.
"An increasing divergence between the results of Protect AF and Prevail is present, and statistically, the results of these 2 studies come from significantly separate distributions, which makes combining the data from Protect AF and Prevail in a Bayesian analysis problematic. Moreover, without incorporating the Protect AF informative prior and based on Prevail data only, the posterior probability of non-inferiority for the first primary endpoint is only 54.4% and for the second primary endpoint is only 48.8%," the agency wrote.
The FDA wants the panel to consider 4 key questions:
- Is the device associated with an acceptable rate of procedure-related complications?
- Does Watchman provide adequate protection from ischemic stroke and systemic embolism in patients with non-valvular atrial fibrillation?
- Is the avoidance of long-term warfarin use after Watchman implantation associated with a reduced risk of hemorrhagic stroke?
- Is there a signal of overall reduced bleeding complications due to the avoidance of long-term use of anticoagulation therapy Watchman patients?
Leerink Partners analyst Danielle Antalffy wrote today that she still thinks the panel will recommend approval for Watchman (the FDA is not bound to follow its panels’ recommendations but often does).
"Given that there were no additional procedure-related events, question 1 is likely to go in Watchman’s favor. But question 2 is likely to drive significant debate, particularly given that 10 of the 13 total ischemic strokes in the Watchman arm occurred more than 1 year after implant," Antalffy wrote in a note to investors. "For question 3, we believe the data is strongly supportive of Watchman given: 1) a significant reduction of hemorrhagic strokes in Protect AF – 0.2 per 100 patient years for Watchman vs. 1.1 for warfarin, albeit in the context of an uncharacteristically poor performance by warfarin compared to other clinical studies; and 2) a significant reduction of hemorrhagic strokes in Prevail – 0.35 for Watchman vs. 0.67 for warfarin. To us, hemorrhagic stroke is of greater concern than ischemic stroke given the high likelihood of associated mortality. And on the last question, while neither Protect AF nor Prevail focused on reduction in major bleeding, the data in both trials signals a reduction in bleeding longer term with Watchman following a higher initial bleeding rate related specifically to the procedure."
Natick, Mass.-based Boston Scientific acquired the Watchman device along with AtriTech for up to $375 million in 2011.
