by Derek Lowe
I wrote here recently about molnupiravir, the unusually potent small-molecule viral polymerase inhibitor that Merck has in clinical trials, and mentioned that it looked like we would only hear about its current results in November or December. I'm glad to report that this prediction was wrong: the trial in early-stage coronavirus patients was stopped early due to efficacy, and the press release came out this morning! That name comes from Thor's hammer, in case you're wondering (Mjollnir), and for once one of these hype names seems to have delivered.
What data we have look quite encouraging: this study (MOVe-OUT) was done in unvaccinated at-risk patients who were newly diagonosed with the coronavirus. These patients had at least one known risk factor for severe disease (obese, 60 years old or older, diabetes, or heart disease), and in the standard-of-care placebo group, 14.1% of these patients (53/377) were hospitalized or died from the disease by day 29 after randomization. Meanwhile, in the treatment group (4 doses/day of molnupiravir orally for five days), 7.3% of the patients were hospitalized (29/385). And interestingly, there were 8 deaths in the control group and none in the treatment group. These numbers - an interim analysis of everyone who had been enrolled as of August 5 - were strong enough, as mentioned, for the independent monitoring committee (which met on Tuesday) to recommend that the trial be halted. Merck says that they will be applying for Emergency Use Authorization as soon as possible. No safety signals were observed (there were more adverse events in the control group), and initial indications are that it was similarly effective against different variants of the virus, including the now-ubiquitous Delta.
This is of great interest for several reasons, and the biggest is that this is a therapy that patients can take themselves, at home. As that earlier blog post mentioned, remdesivir recently showed that it can be useful if given in the earliest states of the disease, but since it's administered i.v., that patient population is not really available to be dosed that way! An oral pill is another matter, though. These are stronger numbers than I expected, to be honest, given that most single-drug antiviral regimens don't reach this level of efficacy. Every positive surprise in this pandemic is to be celebrated.
Merck has another trial ongoing looking at the drug as an outright preventative, where it's being given to people who are at high risk of developing the disease due to exposure to infected patients - after these results, people will be waiting eagerly to see that readout as well. We already know from the first molnupiravir trial results that it's not really effective in people who already have severe disease, so the earlier the better (and you don't get much earlier than not having quite caught the disease yet). But a prophylactic drug has its own complications - how long do you need to keep taking it, and how long can you without side effects, for starters.
People are already wondering if this drug is going to turn into an excuse for people not to get the vaccine. My own take on this is that at this point many of the people who are still vaccine-hesitant probably don't need another excuse. Far too many of them have already decided that they're not getting it, no matter what. But for those who haven't yet and are still wondering if they should, I would recommend looking at those numbers above. Note that Merck specifically was looking at unvaccinated patients, because if the trial had been run in vaccinated ones not enough people would even have been hospitalized yet to be able to tell if the drug was doing anything. If you're in one of those risk groups and you're not vaccinated, you are in the population that a drug company specifically sought out as most likely to end up in the hospital (or dead) if you catch the virus. You can, though, opt out of that group by getting vaccinated: your risk of either one of those outcomes goes down sharply, and what's more, you become less transmissible (and thus less dangerous) to those around you even if you are infected.
So I am still a strong advocate for getting vaccinated, obviously. But that doesn't take away from the news today: this is the first small-molecule antiviral oral therapy that has shown anything like these numbers. Molnupiravir looks like it could keep a lot of vulnerable patients out of the hospitals and out of the cemeteries, and I hope it gets deployed as quickly as possible. Congratulations to the team at Emory that discovered it years ago, to Ridgeback Therapeutics for licensing it for development, and to Merck for putting their resources behind it after that.
https://www.science.org/content/blog-post/molnupiravir-thor-s-hammer-delivers
