A new antiviral treatment that helps suppress replication of the SARS-2 virus is likely to receive Emergency Use Authorization (EUA) by the FDA in the next three weeks. SARS-2 is the coronavirus that causes COVID. This new treatment is a pill made by Merck Pharmaceuticals named molnupiravir, reportedly getting its name from the Scandinavian word Mjölnir meaning Thor’s Hammer. While the name strikes me as a bit presumptuous, the medication does hold promise. Molnupiravir will be marketed under the brand name Lagevrio.
The medication works by inhibiting viral gene production by mimicking one of the genetic building blocks. When the replication process mistakenly inserts the drug then further production of the viral gene is halted. In a double-blinded trial of 750 COVID patients, it was shown to reduce the risk of hospitalization by 50% in those with mild to moderate symptoms (7% hospitalization rate in the treatment group versus 14% for placebo). Treatment must be started within the first 5 days of onset of symptoms. After that, the viral load will have risen to the point that it will not be helpful. The dosing for molnupiravir is one pill twice a day for five days. Its use was approved in the UK earlier this month.
Pfizer is also testing out a medication that has promise, band named Paxlovid, that is a combination of two drugs, one of which is ritonivir. Ritonivir is a drug currently used to inhibit HIV replication, the virus that causes AIDS. The other component in Paxlovid goes by the experimental designation of PF-07321332 as it has not been given a generic drug name yet. Thus, I will refer to the combination by its brand name, Paxlovid. These two drugs in Paxlovid work in a different fashion to molnupiravir by directly shutting down the enzyme responsible for manufacturing viral genes. Paxlovid was shown to be even more effective by preventing hospitalization or death at 89% in a similar group of 1,200 test patients with COVID when compared with placebo. The results were 0.8% of the treatment group experiencing hospitalization or death versus 7% in the placebo group. These two studies are not directly comparable as the molnupiravir study looked only at hospitalization rates while the Paxlovid study used both hospitalization and death as end-points. Like molnupiravir, it must be given early to show effectiveness, in this case within three days of onset of symptoms. It is expected to come before the FDA for consideration of an EUA approval in the early part of 2022.
Both molnupiravir and Paxlovid appear to have minimal side effects. In both studies, the side effects were the same in both treatment and placebo groups indicating that it is well tolerated. They are not approved for use in pregnant women until further research shows their safety in terms of not causing birth defects. This is typical of all new drugs that come out as the bar is intentionally high in that group. There is also a theoretical concern that molnupiravir could cause mutations in human genes because of the way it inserts itself into gene replication. We will only know if this is true or not after we have some years of experience with it. Paxlovid does not carry the same concerns as it works through a different mechanism which is on an enzyme that is specific to viruses.
These treatments will join the monoclonal antibody treatment currently being offered as another option for treating persons with newly diagnosed COVID who are at high risk for developing more serious disease. There several advantages of the two new treatments compared to the monoclonal antibody. A pill is easier to administer than an IV infusion and generally better tolerated by the patient. Paxlovid may be even more effective, although the results seem similar for molnupiravir compared with the monoclonal antibody. The side effect profile is also safer for these pills since the monoclonal antibody carries a small risk of anaphylactic reaction.
It is unlikely that any future variant will develop resistance to these new medications since the mechanism of viral replication is not something that readily mutates, unlike the surface spike protein which is the target of monoclonal antibodies.
It is expected that the initial approval for emergency use will be restricted to persons who are symptomatic with documented COVID infection and who are at high risk for serious illness. However, discussion is already happening that they might also be useful in post-exposure prophylaxis. Thus, it might be given to someone at high risk who got exposed to COVID, but has yet to show any signs of infection. Thereby preventing the virus from taking hold in the first place.
The strategy of giving a pill at the onset of an upper respiratory viral infection to prevent worsening illness is not new. For example, there are several such treatments for influenza. Amantadine was the first, being approved by the FDA in 1976.
Some are hailing these new drugs as potential “game changers”. This may well be true in terms of future deaths, serious long-term illness and healthcare costs given their dramatic ability to reduce hospitalization. I think they will be very helpful additions to our current treatments. However, as with vaccines, the ability to alter the course of the pandemic will depend on the worldwide availability of these drugs. HIV has been around now for a good 40 years with effective antiviral treatments that keep the infection from progressing to AIDS and death being available for at least 30 years. Yet, many parts of the world still are experiencing large numbers of yearly deaths due to AIDS simply because the life saving medications are not available worldwide.
Miller Report for the Week of November 22nd, 2021; by William Miller, MD; Chief of Staff at Adventist Health – Mendocino Coast Hospital
You can access previous Miller Reports by visiting www.WMillerMD.com.
The views shared in this weekly column are those of the author, Dr. William Miller, and do not necessarily represent those of the publisher or of Adventist Health.