Thread by @MonicaGandhi9

Thread on MOLNUPIRAVIR. First, what is this medication? First we should remember, there is not a highly effective outpatient oral treatment for COVID yet. There are tantalizing glimpses into other meds but they are still in clinical trials. So, let's explore this one.

Molnupiravir was not developed for SARS-CoV-2- originally thought of as a broad-spectrum antiviral because it is a "nucleoside analogs". We use those a lot in HIV but they basically inhibit the virus from replicating because this compound interrupts the process of copying

Remdesivir is a nucleoside analog that we use for inpatient treatment because it is intravenous. But what if there was an outpatient oral treatment that you could give to someone like Tamiflu (or in the case of HIV treaters, we give this type of med in combo with others)

Here is a very interesting Bloomberg article about its history and it was being studied as a twice a day oral medication for the treatment of both severe and more mild COVID (to inhibit viral replication of the virus)
bloomberg.com/news/features/…

1st to perform a phase I trial to evaluate which dose you should use (latter also evaluated in phase II trials especially early) but also its safety - usually choose the "maximum effective tolerated" dose-safe at 400, 600 or 800mg twice daily
medrxiv.org/content/10.110…

However, using that dose, the benefit in hospitalized patients didn't seem high and so that trial (called MOVe-IN) did not proceed from phase II to phase III to evaluate it further. This may be because inhibiting viral replication may best be done early on after infection.

However, studies in mild/moderate COVID-19 proceeding. Let's start with a very early phase study (called 2a) in outpatients- not to look at clinical outcomes, but "viral clearance", often a marker will help. Placebo vs 400 vs 800 (both twice daily)
medrxiv.org/content/10.110…

Time to viral RNA clearance decreased & greater proportion overall achieved clearance in those who got 800 mg molnupiravir twice daily (will use BID from now on for twice daily). % of COVID patients who achieved virus negativity in nasal swabs lowest for 800 BID (92.5%) dose

So, the phase II/III trial of molnupiravir BID is proceeding in outpatients (called MOVe-OUT) for those who have had symptoms <5 days & increasing enrollment for those with co-morbidities. Press release here:
businesswire.com/news/home/2021…

And in anticipation, the US government has purchased 1.7 million doses from Merck for US people
merck.com/news/merck-ann…

Okay so preliminary results of the phase 2/3 trial released yesterday at the European Congress of Clinical Microbiology & Infectious Diseases - same results of what was announced by press release April 15 (that MOVeOUT continuing)
businesswire.com/news/home/2021…

In meantime, Hetero (pharm company in India) had entered into a non-exclusive licensing agreement with Merck and put out this press release July 9, 2021. Enrolled 1218 patients with mild COVID within 5 days of symptoms & randomized to 800mg BID vs placebo
heteroworld.com/images/Press_R…

for 5 days. Press release looked at first 741 patients and saw
-Earlier clinical improvement observed in Molnupiravir group compared to standard of care (Day 5 (63.43% vs 22.33%; p=<0.0001), Day 10 (78.96% vs 49.49%; p=<0.0001) and Day 14 (81.55% vs 73.22%; p=0.0150))

*Median time to clinical improvement 8 days in Molnupiravir group compared to 12 days in standard of care alone group (p=0.0001)
* Earlier SARS CoV-2 RT-PCR negativity observed in Molnupiravir group compared standard of care at days 5, 10, 14
• Good safety profile

Fewer hospital admissions in Molnupiravir group compared to standard of care alone (7 (1.89%) Vs 23 (6.22%) p= 0.0027) over 14 days of observation.
No mortality in either group. So, need to see full paper & details but interesting; look forward to MOVeOUT results early October 21

So, doubt we will eliminate COVID in US or elsewhere but control achievable and much easier to treat if early outpatient pill available:

I have interest in increasing trust in public health messaging (this comes from HIV) & so I didn't like the meanness about ivermectin-please message humanely this article explains why it was even considered
washingtonpost.com/lifestyle/2021…

Conclusion: "For those who are anxious, scared, understandable to try to find something,” Parikh said. “But we have something that has already jumped through all the regulatory hoops high-level reviews — and that’s the vaccine.” Merck makes molnupiravir: phase 3 trial data please

Phase 3 trial data on molnupiravir (trial called MOVe-OUT) released TODAY Oct 1: Participants at- risk, non-hospitalized adult patients with mild-to-moderate COVID-19 (had to have at least 1 risk factor for severe disease). merck.com/news/merck-and…

Interim analysis of 775 participants (full trial 1500). Molnupiravir reduced risk of hospitalization or death by ~50%; 7.3% of those on molnupiravir either hospitalized or died through Day 29 (28/385), compared with 14.1% of placebo-treated patients (53/377); p=0.0012.

Through Day 29, no deaths were reported in patients who received molnupiravir, as compared to 8 deaths in patients who received placebo. Other data at IDweek showed molnupiravir active against variants. "Protease inhibitor' under development if needed
reuters.com/business/healt…

for combo treatment in future (to avoid resistance). EUA of molnupiravir to be filed; government purchased doses. Monoclonal antibody data (harder to give, IV or subcutaneous with monitoring) good. With prevention/treatments, easier to achieve endemicity
wsj.com/articles/covid…

Very very exciting news for a simple outpatient antiviral that works for COVID-19!!

Molnupiravir EUA paperwork filed today merck.com/news/merck-and…

Molnupiravir filed with EMA yesterday (short course should not be mutagenic or lead to resistance- 5 days 800mg twice a day) businesswire.com/news/home/2021…

Merck Will Share Formula for Its Covid Pill With Poor Countries - if you read this, will see that the company cites what pharma did during the HIV epidemic to not help provide access to life-saving drugs. So, trying to address that here; important
nytimes.com/2021/10/27/hea…