Thread by @DrEricDing

Major COVID drug bites the dust—Merck’s #COVID-fighting antiviral #molnupiravir failed to prevent #COVID19 hospitalizations/deaths is a large trial of ~25,000 people, despite drug shortening recovery time & lowering viral load. Damn—COVID19 is a tough nut.
statnews.com/pharmalot/2022…

2) Yes #molnupiravir did improve recovery a little— but if you look at the chart, it was mostly just around the 7-12 day mark that the drug had biggest effect, and then the drug seemed to stay parallel and even converge with the placebo group beyond 2 weeks. ➡️benefit didn’t last

3) for the combined endpoint of HOSPITALIZATIONS/DEATHS… no obvious subgroup benefit. There was even a borderline increased risk in the immunocompromised (P for subgroup interaction=0.06, bordeline). Not sure if that is real or bad luck but it’s not good.

4) the shocker is that this trial stands in contrast with the previous trial of #molnupiravir that did show benefit against hospitalization/death. Same dose of 800 mg daily twice a day for 5 days—endpoint assessed at same 28/29 days. Weird.

nejm.org/doi/full/10.10…

5) To be clear - I have no conflict of interest. I do not own Merck stocks nor have I traded any Merck stocks. Drug has been sold on the market since Dec 2021 under an FDA EUA.

Full trial report on the new 25k person #molnupiravir trial from UK:

statnews.com/wp-content/upl…

6) FDA EUA authorized #molnupiravir but with a few caveats: “As a mutagenic ribonucleoside antiviral agent, there is a theoretical risk that molnupiravir will be metabolized by the human host cell and incorporated into the host DNA, leading to mutations.”
covid19treatmentguidelines.nih.gov/therapies/anti…

7) “In addition, there have been concerns about the potential effects of molnupiravir on SARS-CoV-2 mutation rates; the FDA has required that the manufacturer monitor genomic databases for the emergence of SARS-CoV-2 variants.” 👀

➡️This is why many scientists are not big fans.

8) Thus, “The COVID-19 Treatment Guidelines Panel recommends using molnupiravir as an alternative therapy in nonhospitalized patients aged ≥18 years with mild to moderate COVID-19 who are at high risk of disease progression ONLY when (Paxlovid) & remdesivir are not available”