In the last few weeks 2 big pharma companies — Merck and Pfizer — have announced that they are planning to submit antiviral drugs for EUA against SARS-CoV2, following interim analysis of results from Phase 2/3 clinical trials. These drugs could be the first step in a return to normalcy as they could provide an OTC treatment for patients who get covid.
Both Merck’s pill, Molnupiravir, and Pfizer’s pill, Paxlovid, are antivirals that have been developed in the context of other viruses. Given their efficacy in those scenarios their respective companies decided to test them in a covid context and have seen varying degrees of success.
Molnupiravir is a nucleoside analog, i.e. it ‘looks like’ a nucleoside, and on entry into the viral particles will stop replication [Nature]. It was first developed to treat Venezualan Equine Encephalitis Virus (VEEV) before being tested with other coronaviruses. Given positive results in those contexts when the pandemic hit, scientists at Emory University and Ridgeback Therapeutics decided to start testing it for SARS-CoV2.
While clinical trials are still currently underway, the interim analysis (29 days after having had the pill) showed that there was a 50% reduction in the risk of hospitalization or death in covid-positive patients administered with Molnupiravir as compared to the placebo. However, it should be noted that the study only includes patients who have mild to moderate cases of Covid and is agnostic of whether or not patients are vaccinated. (Merck, clinicaltrials.gov)
Paxlovid is a combination of the antiretroviral drug ritonavir and an experimental protease inhibitor. The protease inhibitor acts by blocking the activity of one of the main enzymes involved in replication SARS-CoCV-2–3CL and ritonavir acts to slow down the metabolism of the drug such that it can remain in the system and be effective for longer [Pfizer].
Like with Molnupiravir, clinical trials for Paxlovid are underway, however they have also completed the first 29 days of their trial and have reported the results of their interim analysis. They saw a 89% reduction in hospitalization or death in covid-positive patients. As compared to the Merck study however, it was specified that patients must not be vaccinated, and there is no mention of the severity of cases (unlike for Molnupiravir where they are only testing for mild and moderate cases), although it is mentioned that patients with a ‘History of or need for hospitalization for the medical treatment of COVID-19.’ will be excluded (clinicaltrials.gov).
Our current understanding of the efficacy of these drugs is based on announced interim results and so, from the point of view of the public, it is maybe a little too early to make any definitive conclusions without more information about the results — such as demographic data of the patients, number of patients tested and excluded and more.
However, given that both drugs are orally administered pills, if approved, they could mean an OTC, at-home treatment for covid, and a step towards a true end to our current pandemic. While the information is still rolling in, they’re definitely a light at the end of this rather long, unprecedented tunnel.