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Update on Oral COVID Drugs

Dr. Ted Rosen

Ted Rosen, MD, FAAD, Editor-in-Chief

There are three direct antiviral drugs in various stages of development to combat the COVID-19 pandemic. All these oral drugs interfere with the virus’ ability to replicate within human cells by blocking viral RNA polymerase. As the viral load decreases, the risk of overwhelming inflammatory response also declines. All are aimed at early, outpatient intervention, thereby preventing more serious disease requiring hospitalization.

Molnupiravir (MK-4482)

The drug furthest along in the research sequence is called molnupiravir (MK-4482), which is being developed by Merck and Ridgeway Biotherapeutics. A planned interim analysis of a Phase 3 trial (n = 775) disclosed that 7.3% of at-risk, non-hospitalized adult patients with mild-to-moderate COVID-19 who received molnupiravir were hospitalized through day 29, compared with 14.1% of placebo-treated patients who were hospitalized or died. 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 soon. Additional good news: About 40% of the subjects had their SARS-CoV-2 virus sequenced, and the drug proved equally efficacious across the viral subtypes Gamma, Delta, and Mu. 

PF-07321332 + Ritonavir

Pfizer has developed an oral antiviral drug, PF-07321332, which will be dosed along with ritonavir. The latter agent is designed to slow the metabolism of the anti-viral, allowing it to remain within the circulation for a longer period of time. Pivotal Phase 2/3 studies are underway in non-hospitalized adult participants with confirmed COVID-19 infection who are both at increased risk for progression to severe illness and do not have any risk factors for severe disease. 

AT-527

Roche and Atea Pharmaceuticals are engaged in a randomized, double-blind, multi-center, placebo-controlled Phase 3 trial of their collaborative drug, AT-527. This drug is being studied both in the outpatient and inpatient settings. AT-527 is not only being investigated as a treatment for acute COVID-19 infection, but also as a pre- and post- exposure prophylaxis and as part of the management for so-called “long haul” COVID.

Benefits of Oral Agents

The benefit of oral agents for COVID-19 infections are many. First of all, manufacture is much easier than with monoclonal antibodies and can easily be scaled up to meet demand. Cost should be lower than with monoclonal antibodies due to ease of manufacture. Oral agents are convenient to deliver in both the outpatient and inpatient arenas, and they are easily shipped, allowing for global reach.