I last wrote about the small-molecule antiviral molnupiravir here, and we finally have more information from Merck and Ridgeback about its effects in clinical trials. An interim analysis of the Phase II data from trials in both outpatients and in hospitalized coronavirus patients has been completed, and the news is. . .mixed.

In the outpatient study, Merck says that “The percentage of patients who were hospitalized and/or died in Part 1 of the MOVe-OUT study was lower in the combined molnupiravir-treated groups versus the placebo arm; the number of events reported are not sufficient to provide a meaningful measure of clinical effect.” So that didn’t exactly ring the bells – the lower number could be meaningless, as far as we know. The release does say that viral loads were definitely lower in the treated patients, in a dose-responsive manner, so there’s that. They had 200, 400, and 800mg doses in this study, twice a day, and they plan to move into Phase III at 800mg t.i.d. They’re also changing to bring in only patients who are in the very earliest stages of the infection, and who have other risk factors as well.

Meanwhile, the data from the hospitalized patients were even less encouraging. Merck has decided not to even go ahead with a further phase III in that group, which makes sense if they’re even moving the outpatient selection up to the earliest stages possible.

What I’m seeing here is an attempt to do everything possible in the Phase III to find patients in which molnupiravir will actually show a useful effect. That’s fine, but we need to realize what that means: the “molnupiravir as game-changer” story is probably now dead. There was never too much hope for that one from the beginning, honestly – there are no game-changing single-agent antiviral therapies so far, although one could always hope. The only viral diseases we can really beat down with small molecule therapy are those where we have several specifically targeted drugs, mechanistically distinct, that can be administered at the same time. That’s the case with HIV and hepatitis C. So while we could use a broad-spectrum small-molecule antiviral, we have to be prepared for it not being that great for any particular virus.

And as I mentioned in the last molnupiravir post, keep in mind that this is about as fast as it gets for a new small molecule agent to be deployed in a pandemic. The Phase III is enrolling later this month with the changes above in mind and it will be finished. . .sometime on in the summer? I hope that molnupiravir comes through in that trial and that it shows enough efficacy to be useful. If it turns out to be a drug for high-risk patients to start taking right after they’re diagnosed, then fine, if it really does keep them out of trouble. But that last part needs to be proven.

As several people have mentioned on social media today, Merck is not having a particularly effective time of it during this pandemic. Their two vaccine candidates – neither of them poor ideas prima facie – both wiped out due to lack of efficacy. And in another news release today, they announced that they are abandoning MK-7110, picked up via a buyout of OncoImmune last year. That was a shotgun wedding under the Operation Warp Speed framework – OncoImmune had tried their immune-modulated fusion protein out in a small trial of coronavirus patients, and Merck stepped in to bring more resources into its development.

But that hasn’t worked out, either. The newer  data don’t seem to have been compelling enough, and the FDA has said that they would need more clinical proof before any EUA or approval. Merck has noted that this would put rollout of the drug – if it actually works – on into 2022, and it’s just hard to make the case for that. So MK-7110, formerly CD24fc, is no longer in the pandemic picture. It looks like Merck is out a good amount of money on this deal – they had an OWS contract for $356 million after buying OncoImmune for $425 million, but now nothing will be delivered, and I don’t know what the terms of the contract have to say about that. Under the most generous interpretation, it would seem to be a loss of at least $70 million, but who knows?

I have no idea what Merck paid Ridgeback for rights to Molnupiravir, by the way – as far as I can tell, that figure has never been disclosed. Clinical research is indeed hard, and it ain’t cheap, either.

 

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