What you need to know about molnupiravir, a COVID pill that may come to your local pharmacy

Almost lost in last week’s blockbuster release Omicron: Fear and Disgust — The Rise of the Next Variant It was a recommendation from the FDA Panel to grant an Emergency Use Authorization (EUA) for a drug named Molnupiravir.

This drug is the first of its kind and is a treatment for COVID that can be taken as a pill at home.Its most well-recognized “relative” is Anti-influenza drug Tamiflu (Oseltamivir), it works by blocking the ability of the influenza virus to leave infected cells. When taken within 48 hours of the onset of symptoms, Tamiflu has been shown to reduce influenza intensity and complications, and even death.

The behavior of Molnupiravir (Lagevrio) is a little different. The virus mistakenly inserts metabolites of the drug into RNA. It’s as if one of your computer passwords had an extra number or symbol inserted. Upon substitution, the virus produces a mutated version of itself. This is called a “virus error catastrophe”. The flame goes out because there is no meaningful viral replication.

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Does it work?

Merck, the manufacturer of Molnupiravir, FDA and its MOVe-OUT results A study in which participants were randomized to receive either molnupiravir or placebo. To enroll, participants had to be unvaccinated and had a COVID-19 infection confirmed in the laboratory. Either was calm (Symptoms of influenza but shortness of breath, chest X-ray is normal) Or moderate (Shortness of breath, abnormal chest x-ray, but maintaining oxygen levels in room air).

They also needed to be early in the course of the disease (less than 5 days) and had at least one risk factor to progress to a serious case of COVID. Obesity (77%), age 60 and older (14%), and diabetes (14%) were the most common risk factors in this study.

In October, Merck released data on the first half of more than 1,400 registrants who completed the survey. Only 7% of people who took molnupiravir were hospitalized or, well, died, compared to 14% of people who took placebo. For those who are mathematically challenging, it is a 7% reduction in absolute risk and a 50% reduction in relative risk. (Note: Relative risk can exaggerate profits if the absolute risk is small. For example, crochet beer hats sold on Etsy can reduce the risk of being attacked by an asteroid by 50%. Rest assured .. That’s two to one billion to one billion.)

But when Merck released Final results of last week’s study, The numbers weren’t that snappy. The molnupiravir group maintained 7% levels of hospitalization or death, while the placebo group was better than the first half results suggested, dropping from 14% to 10%. In this study, hospitalization and death were summarized as a single result, but of course they are dramatically different. For the record Nine people died in the placebo group One in every person taking Molnupiravir.

Molnupiravir did not benefit from vaccination. But do unvaccinated people want to take it?

It is important to remember that none of the patients in this drug trial were vaccinated, but that does not mean that they were not in contact with the virus itself. When researchers looked at a small number of test participants who happened to have antibody test results, molnupiravir had no benefit to those who already had antibodies to COVID. (On the other hand, studies of monoclonal antibody therapy seemed to show benefit with or without previous antibodies.)

This raises a clear question with no clear answer. How likely is it to take molnupiravir if someone refuses the vaccine? To answer this, let’s look at some of the safety issues that researchers and the FDA Advisory Board have considered.

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Can Mornupyrabir make new variants?

Although the term “viral error catastrophe” has a good meaning (“Die with COVID, die!”), Can the mechanism of action of molnupiravir (causing RNA mutations) actually backfire?

RNA viruses are notorious banglers when it comes to replication, but they are also part of their genius. Bangling leads to new mutations. Most of those mutations are unexploded, but rare “winners” can continue to create new variants. Omicron’s spike protein has twice as many mutations as delta, but some of these mutations are accidental and may have no biological effect.

Researchers performed viral genetic analysis on a small number of study participants to see if new mutations occurred during treatment. People taking placebo showed spontaneous (“bangling”) mutations in certain infected COVID strains, but taking molnupiravir resulted in a “moderate but significantly higher” mutation rate. It was related.

Outside the lab, what does that mean in real life? To summarize the FDA Advisory Board briefing document: It’s hard to know. They said that the viral shedding could decrease rapidly by the time the molnupiravir-related subspecies appeared in the host, and if the host was unable to spread it, the success story of the subspecies would end there.

However, “impossible” does not mean “impossible”. Even if molnupiravir is very unlikely to cause a mutation (for example, one in a million), if the drug is prescribed in the millions, new variants will probably emerge. According to CNN, The US federal government has already signed a contract to purchase 3.1 million courses of Molnupiravir.

Can taking the drug cause mutations in our own cells?

You might think of DNA as a sacred recipe book, but you need a chef to cook a meal. RNA is for reading recipes and starting cooking. Molnupiravir is designed to interfere only with viral RNA production, but the FDA Advisory Board has pointed out that molnupiravir can be incorporated as a mutation and integrated into DNA.

The Commission found evidence that molnupiravir caused some DNA mutations in bacteria but not in mammals. (Interesting fact: humans have enzymes that repair DNA mistakes / mutations, but not bacteria.) Overall, the Commission states that permanent changes to the recipe book are unlikely. I did.

Molnupiravir was well tolerated, but animal studies suggest that molnupiravir interferes with bone and cartilage formation, as well as fetal development, so the Commission has given drugs to patients under the age of 18 and pregnant women. It was recommended not to administer. Risks and benefits.

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Approval was narrow

If you’ve read it before and are worried about Molnupiravir, the FDA Advisory Board seems to feel the same. They cast 13 votes in favor and 10 votes against recommending it. Pfizer has an oral antiviral drug named paxlovid It works by a different mechanism than Molnupiravir. They have already submitted it to the FDA for an emergency use authorization, and we all hope that paxlovid’s performance and safety profile justifies a more enthusiastic approval vote. stay tuned.