NCHR’s Testimony to FDA on the BrainsGate Ischemic Stroke System

December 10, 2021.

Thank you for the opportunity to speak today on behalf of the National Center for Health Research. I am Dr. Nina Zeldes, a senior fellow at the center. We analyze scientific data to provide objective health information to patients, health professionals, and policy makers. We do not accept funding from drug or medical device companies, so I have no conflicts of interest.

You are asked today whether the BrainsGate Ischemic Stroke System is safe and effective and if the benefits outweigh the risk for use in patients who meet the criteria specified in the proposed indication.

We agree with the many concerns the FDA scientific review highlighted.  I’m sure many of you also have concerns about how to interpret the effectiveness data from the pivotal trial. For example, we all need to be concerned that inaccuracies in the VISTA model prediction may lead to a patient being labeled as a responder even if the treatment had little to no effect.

A 2019 article in The Lancet discussing the pivotal ImpACT24B trial noted that there was no statistically significant difference in 3-month level of disability between treatment and sham groups in the mTTT population. Although the results were more favorable in the CCI subgroup, FDA’s exploratory ITT analysis on the whole CCI subpopulation found an only 6.5% difference in response between treatment and sham, which is below the 7% effectiveness threshold established by the original version of the protocol.

And, while the most favorable analysis of the CCI group found a 10% benefit, we agree with FDA scientists that this is not relevant to the exact version of the device that is currently under review.  In addition to revisions made to the device, the study protocol also changed while the study was underway.

It would not be appropriate for the FDA to approve this device based on a pivotal trial that evaluated a different version of the device that the sponsor intends to market.  We currently have no way to know the true safety OR effectiveness of the device that the sponsor plans to market.  Let’s keep in mind the many safety concerns that the FDA scientists reported, such as microaspiration. The FDA also points out that the device might have serious, albeit uncommon, consequences that may have been under-represented in the clinical studies.

As a final major concern about the data, let’s focus on the number of patients from the U.S. in the pivotal trial. Of the 520 patients in the CCI subpopulation, there were only 31 patients from the U.S – and only 19 received the treatment.  As FDA stated in Table 4 and the related text of their briefing document, and I quote: “In the US CCI population, the success rates were 52.6% and 50.0% for treated versus sham patients.” That’s 10 of 19 and 6 of 12, respectively. FDA noted that “This 2.6% difference between groups” is smaller than it was for patients outside the U.S.  We think you will agree that such a tiny benefit is not clinically meaningful to U.S. patients, and does not support FDA’s approval.

We can all agree that timely, effective treatments are needed in order to reduce disability. But the effectiveness and safety are key, and we agree with the FDA reviewers that the data presented today do not support the claim that the specific device that the company plans to market is either reasonably safe or reasonably effective.

The Neurological Devices Panel voted 7 to 3 that the benefits of the BrainsGate Ischemic Stroke System (ISS500) do not outweigh the risks. 3 abstained.