February 17, 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. Our center analyzes scientific and medical 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.
Today, the committee is asked to assess whether there is reasonable assurance that the Lutonix 014DCB device is effective for the proposed indications. However, the data do not support the conclusion that the device is effective.
The sponsor made numerous changes to the study protocol, which the FDA expressed concerns about. We agree with those concerns. For example, the sponsor reduced the time to assessment of the primary effectiveness endpoint from 12 months to only 6 months. We agree with the Agency Directed Assignment (ADA) panelists that data suggesting a benefit at 6 months without a durable effect at 12 months or later does not provide reasonable assurance of effectiveness of the device.
Furthermore, as the FDA noted, “about 5 years after study initiation, the sponsor elected to terminate the trial with approximately half of the required sample size.” In addition, for those enrolled in the study, there was a substantial amount of missing data for the primary effectiveness endpoint, even at 6 months. We agree with the FDA scientific review that the primary effectiveness endpoint could not be evaluated for those with missing data. Importantly, large amounts of missing data also limits the evaluation of the safety of the device, because outcomes for patients with missing data are unknown.
The FDA did not note any safety concerns expected to exceed those of the current standard of care with non-drug containing devices. However, the FDA also notes that there is uncertainty about safety, given that “outstanding concerns associated with paclitaxel-coated devices should be considered, especially if no compelling benefit is identified.” There is not compelling evidence of benefits for the device, and therefore there are no established benefits to outweigh the potential risks of the device.
We strongly agree with the FDA reviewers’ conclusions in their executive summary, which states that “overall, the limitations associated with the primary and supplementary data make it challenging to draw conclusions regarding the safety and effectiveness of this device.” That’s a polite way of saying there is no clear evidence of effectiveness and insufficient data on safety. It is important to note that the FDA has previously issued 2 “Not Approvable” letters to the sponsor. Having reviewed the available data, we agree with the ADA panelists that there is not enough evidence of meaningful effectiveness of the device. We urge the committee to consider these limitations when voting today, and let the FDA know that you agree that there is no reasonable assurance that the device is effective and therefore no reasonable assurance that the benefits outweigh the risks.
The Circulatory System Devices Panel members voted 15-2, with 1 abstention, to say that the device is not effective and 14-3, with 1 abstention, to say that the benefits do not outweigh the risks. The panel members also voted 15-2, with one abstention, to say that the device is safe.