NCHR Testimony on Vernakalant for Rapid Conversion of Recent-Onset Atrial Fibrillation (Afib)

Nina Zeldes, National Center for Health Research, December 10, 2019.

My name is Nina Zeldes and I am here as a senior fellow to speak on behalf of the National Center for Health Research. Our research center analyzes scientific and medical data and provides objective health information to patients, providers and policy makers. We do not accept funding from drug and medical device companies, so I have no conflicts of interest.

Although there are several treatments for patients with atrial fibrillation, new options that are effective with fewer safety concerns would greatly benefit patients. However, it’s not clear that this drug fulfills those goals.

We strongly agree with the FDA assessment that the new postmarket study data that were provided to alleviate the agency’s safety concerns have not adequately addressed those concerns. We also agree with the FDA analysis that the benefit this drug might possibly provide to a subset of patients does not outweigh the serious risks associated with it.  This is especially worrisome since the subset of patients most likely to benefit hasn’t been clearly defined and because there are other, safer treatment alternatives available to patients.

The new safety data come mainly from one study, SPECTRUM. There are several serious concerns with the study design, which may have contributed to selective enrollment and the underreporting of adverse events. As a post-market, observational study with no control, this is of particular concern.

For example, there were large differences in the rates of serious adverse events reported in the prospectively and retrospectively enrolled patient groups. These large differences seem to be an indication of selection bias, and the fact that patients who had serious adverse events may have been less likely to be included in a retrospective study.

Additionally, this study was not conducted in the United States. It was conducted in Europe, so the patients could differ greatly in terms of BMI, health habits, and access to health care. There was also a lack of diversity: 96% of the patients enrolled in the SPECTRUM study were white. It is therefore not clear how applicable the data are for the US population, which are the patients that are most important to the FDA.

Given the risks and the unknowns, there is no urgency to approve this drug, especially since there are treatment alternatives available. As advisors to the FDA, it is essential that you speak on behalf of patient safety as you carefully consider the data available for how this drug could help or harm patients.

We therefore do not support approval. However, if the majority of you recommend approval, we respectfully urge you to limit the indication to the narrow group of patients for whom the benefit is most likely to outweigh the risks.

Thank you for your time.

The Cardiovascular and Renal Drugs Advisory Committee voted 11 to 2 against approval. You can read more about the meeting here.