Final Remarks on the Molnupiravir Committee Meeting

When mitigating a drug’s side effects is more important than halting approval.

So as it seems, Molnupiravir is being met with either a lukewarm response or with plenty of hesitancy. You would think that in an era of “safe and effective”, when it is difficult to even agree on a novel drug’s safety and efficacy that it should ever see approval.

But here, we see that to be the case with Molnupiravir. For several of the committee members, it seemed more important to have an at-home drug on the market more than many of the uncertainties with respect to genotoxicity.

So how did the committee plan on solving for this? By both limiting the scope of the drug’s use as well as deploying mitigation strategies.

Yes, you read that right! A drug that’s so safe and effective that members of the committee brought up the possible need for mitigation strategies against the drug’s side effects!

Not only does this seem absolutely absurd, it also seems to out of touch which the entire concept of having an at-home therapeutic! Why bother even taking the drug then if there are so many precautions that need to be taken?

Before I get into that, I want to finalize the discussion made about who actually would be able to be prescribed Molnupiravir. I have mentioned it throughout the prior posts, but I want to lay out specifically which groups seem to be the only ones who may end up receiving Molnupiravir.

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Who Gets to take the Drug

Nearly the entire committee, as well as Merck, seem to follow the criteria put forth by the CDC for the highest risk demographics which usually includes the elderly, immunocompromised, and people with several underlying conditions. Here, I’ll dissect the groups overall and we’ll see how limited the demographics of those prescribed Molnupiravir will be.

• Pregnant women/ people expecting to get pregnant: This was pretty much all over the place. Merck suggests not providing this drug to pregnant women. Some members suggested that they couldn’t stop a pregnant women from taking it if she wants to, while others said extreme monitoring practices should be put into place such as counseling, black box labeling on Molnupiravir, or even through the use of a surveillance app. A few have argued that, under no circumstances, should pregnant women take it. Extrapolate that to lactating women, and even to any men or women who want to have children and then it seems like the only way to get around this concern is to provide this drug to older, post-menopausal women and elderly men. Now, I am not a doctor, but I have argued against the prescription in pregnant women due to the uncertainty. If anything, Molnupiravir may follow the same exclusionary criteria as the clinical trial.

Taken from the clinical trials information. Click on the image to enlarge.

• Age (Adults or those over 60 only?): Again, uncertainties arise when it comes to age. Now, remember that studies were never done in those under 18. Pair that with concerns about early growth plate ossification, as well as the general low-risk of COVID in younger demographics and I see no valid reason to provide Molnupiravir to anyone but adults. Now, the concern then comes up with people who may want to have kids and the uncertainty with alterations to gametes, meaning that those who are not within birthing age are going to be the best candidates to remove that uncertainty. The cutoff of 60 was brought up since Merck’s study showed good results in those over age 60. So either all adults will be provided access to Molnupiravir with strong caveats for younger adults, or only those over 60 will be provided it. It seems at this point it’d be easier just to say who CAN’T get the drug.

• Underlying conditions and comorbidities: Fortunately, Merck included patients who had several comorbidites into their studies. However, their own results suggested that in those with diabetes and several comorbidities Molnupiravir did worse than placebo. Members of the committee wanted Merck to look into these questionable results. Nonetheless, those with undelrying conditions seem to be the best drug candidate. This includes those who are obese, diabetic, have heart conditions, and things of that nature.

• Unvaccinated: This seems like a strange group (are they trying to target a dangerous drug towards the unvaccinated?), but it seems like this follows the logistics of the study. It seemed that the unvaccinated were considered a high-risk group, although no one vaccinated were allowed to participate in the study. I would argue that it seemed they wanted to get rid of that confounding variable more than to target the unvaccinated. Discussions were brought up with trying Molnupiravir in vaccinated individuals so that data could be collected, but for now the unvaccinated will be the most likely to receive Molnupiravir.

• Immunocompromised: As of now the evidence isn’t there yet to prescribe Molnupiravir to those who are immunocompromised, although they are the most likely to benefit from a nucleoside analogue. Vaccines may not be able to elicit a robust immune response, and Mabs may add selective pressure onto SARS-COV2 that may lead to escape variants. However, no comprehensive studies were done by Merck in those who have weakened immune systems, and many members wanted to see more studies before considering this group.

• For more risk mitigation strategies refer to the FDA’s Briefing Document, although do note that some of the topics discussed only occurred in the meeting and may be missing from the document.

So as it seems there are more exclusions than inclusions. As the meeting went on it seemed like the window of participants continued to get more narrow, and eventually at the end it seemed like hardly anyone would fit the criteria for Molnupiravir.

Just to highlight this point even more, a remark was made about when Molnupiravir may be used in a pregnant woman.

A comment was made that a possible candidate for this drug would be a pregnant woman in her 40s, obese, with a heart condition and diabetes. Under such circumstances, the risk of SARS-COV2 may be considered more concerning than the possible genotoxicity, but what a unique circumstance to consider!

But let’s take a look at something even more alarming. Keep in mind the phrase “safe and effective”, as it’s been driving many of the discourse around COVID. But what happens when a drug’s side effects may be so severe that you may need to protect other people from it? Let’s find out!