NCHR’s Testimony to FDA About Molnupiravir for COVID-19

November 30, 2021

Thank you for the opportunity to speak today on behalf of the National Center for Health Research. I am Dr. Meg Seymour, 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 being asked to assess whether the known and potential benefits of molnupiravir (MOV) outweigh the known and potential risks for those who are at high risk of severe COVID-19 infection. However, the balance of benefits and risks may differ between different types of patients, and not all types of patients were studied.  

Let’s start by talking about vaccination. All patients in the study were unvaccinated. Should it be approved for vaccinated patients as well? Almost 60% of the U.S. population has been fully vaccinated, and many of them still have antibodies to the virus. The sponsor’s data indicate that MOV patients with antibodies to the virus did no better than placebo. Without data on vaccinated patients, there is no way to know the safety and effectiveness of MOV for vaccinated patients, and yet you are being asked to vote on whether MOV should be authorized for all patients at risk, which includes the vaccinated. The FDA’s proposed Fact Sheet for Healthcare Providers does not mention that the drug has only been tested on the unvaccinated. That limitation of the data needs to be noted and made clear to healthcare providers, who are otherwise likely to prescribe the drug for all patients, not just unvaccinated patients. 

The study also only examined those with pre-existing conditions that are known to be risk factors for severe COVID-19. Drugs should not be used for populations that they are not tested on, due to unknown safety and effectiveness in unstudied populations. If authorized, what would FDA do to restrict the use of MOV only to the patients most likely to benefit?

There are other patient groups that should be excluded from an EUA. We agree with both the FDA and the sponsor that because of the potential developmental risks, MOV should only be used in those 18 and older. Given the findings from animal studies about the fetal toxicity of MOV, we are not convinced that the known and potential benefits of MOV outweigh the known and potential risks of MOV in pregnant individuals. For that reason, if an EUA is granted today, it should not be authorized for pregnant patients. We also support the FDA’s suggested protocol for lactating patients. 

Finally, let’s focus on the overall safety and effectiveness of MOV. Although the relative risk reduction for those taking MOV compared to placebo is described as 30%, there is only a 3% absolute difference in incidence of hospitalization or death between the two groups. Since the patients in the study were selected to be the most at risk of severe COVID-19 due to their unvaccinated status and underlying health conditions, a 3% reduction in hospitalization or death seems to be a rather small benefit for any individual patient. As noted in other data provided by the sponsor, the benefit may be even smaller for patients who are vaccinated, under 60, and/or who have no underlying conditions.

Given that modest benefit, the unknown risks should be of greater concern. FDA notes in the briefing document that the safety sample is relatively small compared with that of other COVID-19 treatments granted EUAs. Even with the additional data presented today, is the safety sample large enough to evaluate rare but serious side effects? Unfortunately, it is difficult to determine which AEs in the study were caused by the drug and which were probably a symptom of COVID-19 infection. Given the modest benefit and the much greater range of patients that may take MOV if it is authorized, how confident are you of the proven benefits vs. risks of this drug?  

There is a need for COVID-19 treatments, especially those that could prevent hospitalization and death. However, the scientific standard should be authorizing and prescribing drugs only for the types of patients that have been studied. We urge you to consider these unknowns as you consider your recommendations today.