The FDA’s Circulatory Systems Devices Panel voted 13-1 yesterday to recommend approval of Boston Scientific‘s (NYSE:BSX) Watchman heart implant for reducing the risk of stroke and systemic embolism.

The panel voted 13-1 in favor of safety, effectiveness and Watchman’s benefits outweighing its risks, with some modifications to Boston Scientific’s proposed indications for use, label and post-market study of the device.

The news sent BSX shares up 3.3% to $11.55 apiece as of about 3:30 p.m. today.

Watchman is a percutaneously delivered permanent cardiac implant, designed for implant in the heart’s left atrial appendage to prevent thromboembolism. Boston Scientific is seeking indication to treat patients with non-valvular atrial fibrillation who are eligible for warfarin therapy based on CHADS2 or CHA2DS2–VASc scores.

The emphasis of clinical trials for Watchman was on preventing embolism, stroke and related mortality in active patients. The device can provide a better quality of life than drug anticoagulation therapy, which can limit a patient’s ability to perform certain tasks for fear of injuring themselves and having a life threatening bleed, panelist Dr. John Somberg of Rush University Medical Center said.

The panel was tasked with discussing and voting on whether Watchman can now be approved based on the results of the Prevail trial and additional long-term follow-up data from the Protect-AF study, especially regarding the proposed indications for use and the proposed post-approval study. Data from the Prevail study hit 2 of the 3 primary endpoints for safety and effectiveness, but failed to demonstrate any improvement in rates of stroke, systemic embolism and cardiovascular or unexplained death at 18 months between patients who received the Watchman device and those who were treated only with warfarin, a blood thinner.

Although several panel members said they harbored ongoing concerns about Watchman’s failure to meet its primary non-inferiority endpoint in Prevail, the panel overall was persuaded by the totality of the data and believed that there was an acceptable distribution of the data points, which they said were consistent with a favorable response to the device.

Panelists generally agreed that new data presented in the CAP registry and Prevail trial appropriately address the original concerns about acute Watchman implantation procedural outcomes and noted that this was verified by reduction in the event rate in both the device group and the control group.

"There remains a requirement for a post-approval study to continue to follow these event rates," stressed panel chairman Dr. Clyde Yancy of Northwestern University’s Feinberg School of Medicine. "The improvements appear to be largely dependent upon an effective education program, which the sponsor has created, which should be mandatory going forward, and it should include descriptors or attributes of centers that are most likely to replicate these results."

The proposed indications for use for the Watchman device are not acceptable without modification, some panelists said. In addition to what has already been proposed, Boston Scientific should work with the FDA to specify in the IFUs that a "personalized approach" be used in employing this technology "so that it is in keeping with the patient’s wishes, lifestyle and risk and this is in the context of the known concerns we have about the potential for adverse events," Yancy said.

Panelists asked that the labeling for Watchman include some indication of "reasonable survival" for the device due to data showing that some exposure to the device is necessary before the stroke risk is ideally modified. The labeling should also highlight that ineligibility to take anti-coagulation therapy should be a contra-indication for the device, they said. And the panel wanted the Watchman label to be consistent with clinical trials, including a description of anti-coagulation regiments followed by anti-thrombotic regiments, and wanted it to provide detail about what center and physician practices led to successful implantation.

The panel also asked for some modifications to the proposed post-approval study for Watchman.

"It is appropriate for us to have the post approval study, and it is reasonable for this to be a single-arm study with performance goals that are informed by the previous experience with the data. Importantly, there is unanimous opinion that the sample size ought to be larger, and there is an expectation that the recruitment would be consecutive, and that there would be a more representative patient population that reflects those that actually experience the disease," Yancy said.

“We are pleased with the outcome of today’s panel, which represents an important milestone toward making this innovative technology available to patients with AF at higher risk for stroke who need an alternative to long-term warfarin therapy,” Dr. Kenneth Stein, Boston Scientific’s chief medical officer, said in prepared remarks. “We appreciate the opportunity to present our comprehensive data supporting the Watchman technology and look forward to continuing discussions with the FDA regarding the panel’s comments.”

Yesterday’s panel wasn’t Boston Scientific’s 1st bite at the apple. The FDA in March 2010 issued a "not approvable" letter for the device, ruling that existing data failed to demonstrate a reasonable assurance of safety and effectiveness despite a positive panel vote the year before. The agency ceded that the LAA closure device showed potential clinical benefit in the Protect-AF trial.

In its 2010 denial, the watchdog agency cited a handful of problems with the Protect-AF trial, including that the study enrolled a substantial number of study subjects who may have been acceptable candidates for aspirin therapy rather than anticoagulation. The FDA also flagged the concomitant use of chronic clopidogrel therapy in both study groups (51% of follow-up time in device subjects and 16% of follow-up time in control subjects) and said that device implantation raised safety concerns such as pericardial effusion and air embolism.

Boston Scientific, in collaboration with the FDA, designed the Prevail study to address the limitations of the Protect-AF data. The agency, recognizing the value of the safety and effectiveness information captured in Protect-AF, co-developed with Boston Scientific a Bayesian study for Prevail in which a portion of the Protect-AF data could be used as an informative prior to collecting additional safety and effectiveness data on Watchman. In addition to new data collected in Prevail, continued follow-up of Protect-AF subjects was collected to provide critical insights into long-term device safety and effectiveness.