November 9, 2022
Thank you for the opportunity to speak today on behalf of the National Center for Health Research. I am Dr. Ealena Callender, a physician with a master’s in public health. I am a Senior Fellow at our nonprofit think tank. Our center conducts, analyzes, and scrutinizes research on a range of health issues, with a particular focus on which prevention strategies and treatments are most effective for which patients and consumers. We do not accept funding from companies that make products that are the subject of our work, so we have no conflicts of interest.
Every day, hundreds of men and women die due to COVID-19. In the third year of this worldwide pandemic, we are still searching for safe, reliable, and effective treatments for severely-ill patients. Initial data for Veru’s drug Sabizabulin is promising, but the study leaves unanswered questions about safety and efficacy. The question for you is whether better evidence is needed before emergency use authorization is granted.
Veru’s multicenter placebo-controlled phase 3 clinical trial found a significant reduction in mortality for patients in the treatment group. The lower mortality rate was impressive: 20.2% (19 of 94) for sabizabulin versus 45.1% (23 of 51) for placebo. But, the strength of this data remains unclear due to the relatively small size of the study – the analysis included only 94 patients in the treatment group and only 51 on placebo.
The placebo group seems to have an abnormally high mortality rate. They were older, had a higher WHO severity score, and were more likely to have diabetes, hypertension, and heart failure. All of these could have caused the higher mortality rate compared to sabizabulin. This makes it impossible to determine if the placebo group experienced a higher mortality rate because they had more risk factors for severe disease or because they did not receive treatment with sabizabulin.
Small study size may produce false-positive results or an overestimate of the magnitude of an association. Also, with so few patients, it is impossible to determine if there are relatively rare but serious side effects.
Medical products may be considered for EUA if they “may be effective” to “prevent, diagnose, or treat serious or life-threatening diseases” caused by COVID-19. In addition, FDA requires that the benefits outweigh the potential risks of the treatment and that there is “no adequate, approved, and available alternative to the candidate for diagnosing, preventing or treating the disease or condition.”
The evidence presented today is obviously stronger than the evidence for some previous COVID EUA treatments, such as hydroxychloroquine. But we are in a different situation today, because we have several different safe and effective vaccines to help prevent severe illness, hospitalization, and death from COVID-19. Moreover, there are treatments available to help manage severe illness in patients hospitalized with COVID-19. The drugs in use today have been studied and used on thousands of patients thus far. While there may be some uncertainty about their risks or benefits for specific types of patients, they have been studied in much better-designed research than the one small study of Sabizabulin.
When we have multiple options to offer patients for both prevention and treatment, should FDA authorize the use of a treatment based on a comparison with a placebo group that is at higher risk of mortality in so many important ways? Is it appropriate to spend millions of dollars on a treatment that isn’t yet proven to work? Would a reasonable compromise require the company to start enrolling patients in a study of a better-matched placebo group prior to making an EUA decision? Unfortunately, it would be very difficult to conduct a confirmatory study once Sabizabulin is on the market. For that reason, we urge this committee to recommend the FDA require better data before granting emergency use authorization for this drug.
The committee voted 8-5 that the known and potential benefits of sabizabulin do not outweigh the known and potential risks for the treatment of adults hospitalized with COVID-19 who are at high risk of ARDS .