1/11 Shocking and terrible news, possibly for the entire world. Molnupiravir works by inducing mutations in the virus. The potential danger is obvious, and Merck has not provided any reassuring data on this.
https://twitter.com/michaelzlin/status/1474030344328204288
2/11 Perhaps most shocking is that MOV was approved when it's not at all clear that it will have any benefit at all for the people taking it. MOV only showed any efficacy at all in the pre-Delta era. nature.com/articles/d4158… 
3/11 The @Nature article above actually understates the matter. In the second part of the trial, from Aug-Oct, there was actually a 32% higher rate of hospitalization in the MOV group than in the placebo group (6.2% vs 4.7%).
4/11 Merck had no explanation for why molnupiravir appeared to be worse than useless in the last half of their trial. However, it seems likely Delta rendered it useless.
5/11 Why was molnupiravir useless—or perhaps even harmful—against Delta? Apparently, no one at the FDA thought to ask this question. Could it be due to Delta's rapid replication? If so, MOV will likely prove useless against the rapidly replicating Omicron.
6/11 As @jpogue1 points out, the hospitalization rate in the placebo group in the interim analysis was a real outlier and should've raised eyebrows.
https://twitter.com/jpogue1/status/1464371651164966921
7/11 Merck showed that MOV decreased viral load 100-fold in hamsters, but this is not reassuring at all. That means there was still a ton of mutated virus present in the hamsters.
https://twitter.com/michaelzlin/status/1473848539394363392
8/11 But the situation is actually substantially worse that the hamster data show. According to Merck's own FDA presentation, the decrease in viral load by days 3 & 5 in the MOV group compared to the placebo group is a modest 42 and 53%. It gets worse. fda.gov/media/154472/d…
9/11 The human trial data show no difference in viral RNA titers at day 29 in treatment group compared to placebo. Figure buried in supplementary data. Perhaps I'm misinterpreting something, but this doesn't seem reassuring to me.
https://twitter.com/victoriacyanide/status/1474109139596972035
10/11 A full course of molnupiravir requires taking 40 pills over 5 days—not an easy regimen. It is 100% certain that many patients—many of whom would improve even without treatment—will not finish the full course. The FDA freely admits the danger in this.
https://twitter.com/michaelzlin/status/1474110547750645769
11/11 Finally, while it is probably a coincidence, it is noteworthy that of the 173 molnupiravir trial sites, four were in Gauteng Province, South Africa, the cite of the first major Omicron outbreak. There were eight other South African sites also. clinicaltrials.gov/ct2/show/NCT04…
12/ When I made this thread, I hadn’t read the article below by @WmHaseltine, former professor at Harvard Medical School & Harvard School of Public Health & founder of two Harvard research departments (biochemical pharmacology & human retrovirology). forbes.com/sites/williamh…
13/ Haseltine points out that at the clinical trial sites in South Africa (including 4 in Gauteng), molnupiravir was sometimes used in small doses of exactly the sort expected to induce mutations without clearing the virus from the body—the nightmare scenario.
14/ FDA and Merck both admit that the risk of onward transmission from MOV-treated patients exists if patients do not isolate & complete the 5-day, 40-pill course (or, presumably, take a lower dose). This is guaranteed to happen on a massive scale.
https://twitter.com/michaelzlin/status/1474109931859046402
15/ But most worrisome of all, the majority of the mutations found in Omicron are of exactly the type molnupiravir is known to preferentially induce. And the number of mutations in Omicron is consistent with the number observed in other coronaviruses exposed to molnupiravir.
16/ Why in the world was this drug, which might have zero benefit for patients (see tweet #3) and which might unleash a hellish menagerie of variants on the world, approved by the FDA? This is madness. It must be reversed.
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