An F.D.A. panel endorses Merck's Covid pill for high-risk adults.

[BumRushDaShow]

Source: New York Times

An expert committee on Tuesday voted to recommend that the Food and Drug Administration authorize a Covid pill from Merck for high-risk adults, the first in a new class of antiviral drugs that could work against a wide range of variants, including Omicron.

The drug, known as molnupiravir, has been shown to modestly reduce the risk of hospitalization and death, predominantly from the Delta, Mu and Gamma variants. The expert panel recommended it for Covid patients who are older or have medical conditions that make them vulnerable to severe illness. The pill could be authorized in the United States within days, and available by year's end.

In the coming weeks, the F.D.A. may also greenlight a similar pill from Pfizer that appears to be significantly more effective than Merck's. Health officials around the world have been counting on the new pills to reduce the number of severe cases and save lives. If Omicron causes a surge in severe infections, it could make them even more important.

Scientists have yet to run experiments to see how well the pills block Omicron viruses from replicating. But there are reasons to think they would remain effective even if the variant can sometimes evade vaccines.

Read more: https://www.nytimes.com/2021/11/30/health/fda-merck-pill-molnupiravir.html

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Short article as it is breaking (they just had the vote). Vote was 13 YES - 10 NO.

[Tomconroy]

1. Here's an article that outlines some of the issues discussed:

https://www.nbcnews.com/news/amp/rcna7107#aoh=16383098833097&referrer=https%3A%2F%2Fwww.google.com&_tf=From%20%251%24s

[BumRushDaShow]

2. The meeting just ended around 15 minutes ago - 5:33 pm EST

I have been watching since 9 am.

The Chair was laughing about it being the first time one of these meetings "went over time" since he has been Chair.

I have issues with this myself though - mainly the mechanism of how the drug works, which is to basically disrupt the sequences of the DNA that gets replicated during the reproduction cycle. But the possibility exists that there may be unintended consequences of that disruption (by I think, introducing different amino acid sequences into the viruses chains with the hope that they will damage that DNA and help to self-destruct the virus).

I.e., the danger is that you may get some sequence that gets creared that doesn't self-destruct the virus but causes some viable mutated version of the DNA (what they are called "mutagenesis" ).

From what was reported by Merck, the research didn't really identify that as a problem when used "in vivo" (i.e., within a living organism like mice or humans), but in some standard biologic test regimes, was found to be seen happen to some degree "in vitro" (or as the old saying goes - in the petri dish).

I figured the vote would be close and I expect there will be all kinds of caveats and narrowing of who this might be recommended for when CDC reviews the data. FDA mainly only looks at whether the product is "safe and effective", whereas CDC delves more into the use of that product in treatment of medical conditions and does the main recommendation for who benefit the most from it.

[Tomconroy]

3. Do you think Pfizer will do better?

[BumRushDaShow]

4. Pfizer's claims have been to have higher efficacy

Merck's efficacy was revised lower just days before this meeting -

FDA advisory group to review safety and efficacy of Merck's Covid pill

Nov. 29, 2021, 10:19 AM EST
By Berkeley Lovelace Jr.

(snip)

Results released Friday by Merck showed the drug reduced the risk of hospitalization and death among high-risk Covid patients by 30 percent. That’s down from an estimate of 50 percent the company made in October, and lower than currently authorized monoclonal antibody treatments, which have been shown to reduce the risk of severe outcomes from Covid by at least 70 percent.

(snip)

https://www.nbcnews.com/health/health-news/merck-covid-pill-fda-advisory-group-review-safety-efficacy-rcna6868

Will have to see what Pfizer presents for their product. FDA's ADAC hasn't scheduled for them yet since they just submitted for an EUA a couple weeks ago.

I think the concern that was bubbling around the Committee was -

1.) Pregnant and/or child-bearing women
2.) Severely immuno-compromised (vs "high risk" ) where the issue was that the virus tends to linger longer in that population and thus potential stray viral mutations, that could be enhanced by the drug, might be worrisome - and mainly because the drug is recommended for people who would NOT need to be "hospitalized" (it is to avoid the hospitalization where they can convalesce at home) and who could come into contact with family members and others, possibly passing on some mutated version of the virus

So there is a desire not only for more data over a longer term, but some way to offer mitigation for any stray mutations (which might obviously mean use as a combo drug with other meds, which is what Pfizer's proposed treatment course will do).

I do get that all of this is an attempt to throw as many things at this problem as they can and this is really all the "sausage making" to do that, something that is rarely discussed in the public domain.

[LisaL]

5. Much higher efficacy for Pfizer if 89% for preliminary results holds.

Merks latest number is only 30% reduction.

[BumRushDaShow]

6. Since they apparently started their trials before Pfizer

they have been hanging their hats on an 'independent data monitoring Committee" and FDA recommending they end their trials recruitment "early" and start submitting their application, with the supporting data, for an EUA -

Merck and Ridgeback’s Investigational Oral Antiviral Molnupiravir Reduced the Risk of Hospitalization or Death by Approximately 50 Percent Compared to Placebo for Patients with Mild or Moderate COVID-19 in Positive Interim Analysis of Phase 3 Study

October 1, 2021 6:00 am ET

At the Interim Analysis, 7.3 Percent of Patients Who Received Molnupiravir Were Hospitalized Through Day 29, Compared With 14.1 Percent of Placebo-Treated Patients Who were Hospitalized or Died

Merck Plans to Seek Emergency Use Authorization in the U.S. as Soon as Possible and to Submit Applications to Regulatory Agencies Worldwide

If Authorized, Molnupiravir Could be the First Oral Antiviral Medicine for COVID-19

(snip)

At the recommendation of an independent Data Monitoring Committee and in consultation with the U.S. Food and Drug Administration (FDA), recruitment into the study is being stopped early due to these positive results. Merck plans to submit an application for Emergency Use Authorization (EUA) to the U.S. FDA as soon as possible based on these findings and plans to submit marketing applications to other regulatory bodies worldwide.

(snip)

https://www.merck.com/news/merck-and-ridgebacks-investigational-oral-antiviral-molnupiravir-reduced-the-risk-of-hospitalization-or-death-by-approximately-50-percent-compared-to-placebo-for-patients-with-mild-or-moderat/

The one thing about their trials was that they were done with people who were all unvaccinated. So there really is no data about use of the product with anyone who was vaccinated. In a way, that is an interesting "control group" if you look at having further trials down the road with anyone who was vaccinated but experiences a more moderate breakthrough infection (particularly those who are high-risk whose immune systems aren't up to snuff - even with the vaccine primary series (and boosters if needed)).