Thread by @DrEricDing

💡BREAKING—New oral anti-viral drug *molnupiravir* cuts risk of #COVID19 hospitalization and death **in HALF** in a randomized trial. Results so astounding that the trial is being stopped early, and Merck plans to apply for emergency authorization ASAP. 🧵 washingtonpost.com/health/2021/10…

2) An independent board of experts monitoring the trial recommended the study be stopped early because of the positive (beneficial) results, a significant and telling step in a study. Merck & Ridgeback Biotherapeutics said they would apply for EUA for molnupiravir in the US ASAP.

3) It would be the first antiviral pill for covid-19. A simple, easy-to-prescribe pill that prevents mild and moderate cases of covid-19, from turning into dire episodes has been one of the missing pieces of the medical armamentarium to fight the virus.

4) Why is it so big? Other drugs like “Monoclonal antibodies are expensive, tricky to manufacture and cumbersome to administer, requiring infusions or injections. Vaccines have been remarkably effective, but access is limited in much of the world.” This antiviral is much easier.

5) Merck has already begun producing molnupiravir. The small brown capsules must be taken twice a day for five days. The company predicts producing 10 million courses of treatment by the end of the year.

6) The U.S. government made an advance purchase of 1.7 million doses of the drug at a cost of $1.2 billion.

7) If cleared, Merck’s drug would be the first pill shown to treat COVID-19, a potentially major advance in efforts to fight the pandemic. All COVID-19 therapies now authorized in the U.S. require an IV or injection.
apnews.com/article/a9a224…

8) Merck and its partner Ridgeback Biotherapeutics said early results showed patients who received the drug, called molnupiravir, within five days of COVID-19 symptoms had about half the rate of hospitalization and death as patients who received a dummy pill.

9) The study tracked 775 adults with mild-to-moderate COVID-19 who were considered higher risk for severe disease due to health problems such as obesity, diabetes or heart disease.

10) Among patients taking molnupiravir, 7.3% were either hospitalized or died at the end of 30 days, compared with 14.1% of those getting the dummy pill. There were no deaths in the drug group after that time period compared with eight deaths in the placebo group.

11) The results were released by the company and have not been peer reviewed. Merck said it plans to present them at a future medical meeting.

12) The biggest impact of the drug might be in the rest of the world, where vaccine availability is low & monoclonal antibody treatments may be impractical. Merck has licensed its drug to 5 Indian generic drug makers to speed up availability in low- & middle-income countries.

13) “The company said it would use a “tiered pricing approach,” pricing the drug to reflect countries’ ability to pay for the drug.” ➡️ will have to see what this means in reality.

14) Lab & animal experiments suggest the pill may be effective against known variants, including delta. Unlike vaccines or antibodies that target proteins on the surface of virus, molnupiravir works by introducing nonsense mutations & garbling the coronavirus’s genetic 🧬 code.

15) That means it may be more resistant to mutation, and may even work on other coronaviruses or RNA viruses. Thus this has the “potential to have a drug that could work across multiple coronaviruses.” ➡️ could work for future coronavirus pandemics!!

16) the success of this new drug against #COVID19 came from careful smart research investment. The Biden administration directly invested $1.2 billion in early June 2021 - they pre-paid for the drug development and its pre purchase!

washingtonpost.com/health/2021/06…

17) Researchers in @GeorgiaStateU in Atlanta first reported success of the drug against the #SARScov2 coronavirus in ferrets! They were funded by the @NIH, not by pharma. The authors (Robert M. Cox, Josef D. Wolf & Richard K. Plemper) have no conflicts!
nature.com/articles/s4156…

18) Furthermore, Vanderbilt scientists @DenisonLab @Ardinajp helped in developing this drug approach too in 2020…

And the @VUMChealth research was supported by National Institutes of Health @NIH grants.
news.vumc.org/2020/04/06/vum…

19) I’m hopeful. Though data still need to be published. That said, 50% efficacy against hospitalization & death is good— but not as high as a vaccine’s 90-99% efficacy against severe #COVID19 & death. ➡️Vaccine’s lowering risk 10-100x is better than this drug’s 2x! Perspective.

20) Many folks asking if stopping a trial early for good results is a good idea or not… as someone who does trials for a living (and have a COVID prevention trial that I am running myself)— the reason for stopping a trial early for positive results is because of bioethics…

21) Why? Well imagine you’re in the PLACEBO (dummy pill 💊) control group… and you are sick with COVID… and the trial continued now knowing that the drug could save your life— it is now **unethical to withhold the drug** from you. This is the main reason - to save lives.

22) These modern bioethics reforms for trial were developed after controversies in the past about withholding treatment that is proven to save lives. It’s just not ethical to withhold it once you have demonstrated it can save someone’s life. Compassion for placebo volunteers. 🙏

23) However, there is some caveat— @PeterHotez and @RickABright are slightly concerned this drug is not appropriate for pregnant women. And it’s likely better by prescription than over the counter.

https://twitter.com/peterhotez/status/1443898540573536263

24) Another hopeful news for this drug — it could maybe help clear #LongCovid chronic infection in the brain… Molnupiravir crosses the blood brain barrier - and could clear #COVID19 there. Hopeful - let’s see!

https://twitter.com/njbbari3/status/1443917309467262976

25) For those sticking with “natural immunity” instead of vaccines… Molnupiravir only reduces risk of dying by 2x, while remember the vaccine reduce risk of death by 10-100x. Vaccines still better, cheaper/free! ➡️ Also, vaccine superior than natural for breakthroughs! See👇

https://twitter.com/drericding/status/1443411199920594956

26) Fun fact— The name of the new drug molnupiravir is a reference to Thor’s hammer, Mjölnir! (And a drug ending with -vir means it’s an antiviral drug).

27) And while $700 for a course of molnupiravir pills isn’t exactly cheap—a transfusion alone can cost $1,000, & that’s on top of the cost of drugs delivered intravenously. A course of monoclonal antibodies can cost $2,100, while remdesivir can cost $3,100
vox.com/22704265/merck…

28) I want to add— Merck had no decision power over stopping the trial early. It was decided by an independent panel of outside medical experts - and it was stopped early not for safety but for compassionate ethics to not withhold a lifesaving drug. It was for a very good reason.