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An antiviral pill for COVID-19 — is molnupiravir too good to be true?

In the spring of 2020, scientists around the world were throwing everything they had in their freezers onto petri dishes, along with human cells and SARS-CoV-2, the virus that causes COVID-19. The goal was to find agents capable of protecting the cells from this novel virus, and many drugs were found sufficient in these in vitro experiments — hydroxychloroquine, ivermectin, and some HIV antiviral drugs among them. But protecting cells in a petri dish often does not translate to clinical benefits in patients. Many of the promising drugs from in vitro experiments have failed or provided inconclusive results in clinical trials, and some remain under investigation.

One agent that was found effective at improving recovery among patients with COVID-19 is an antiviral drug called remdesivir. First described in 2016, remdesivir was a promising drug with previous in vitro effects against Ebola, MERS-CoV, and SARS-CoV-1, and then it was found to inhibit SARS-CoV-2 as well. COVID-19 became the first FDA-approved indication for remdesivir in October 2020. Remdesivir (brand name Veklury) was the first medication authorized specifically for the treatment of COVID-19 with conditions by Health Canada in July 2020. However, remdesivir is only recommended for hospitalized patients with severe COVID-19, leaving patients with mild-to-moderate COVID-19 with only intravenous infusion of monoclonal antibodies as a treatment option.

The most recent drug to enter the COVID-19 treatment race is another new antiviral: molnupiravir. Molnupiravir is similar to remdesivir in its mechanism of action. Both drugs inhibit the viral RNA polymerase, thereby blocking the ability of the virus to replicate itself. Originally investigated for influenza, it was tested on SARS-CoV-2 early in the pandemic and, like remdesivir, was found to prevent growth of SARS-CoV-2 in vitro.

Molnupiravir is an oral pill given twice daily for five days, which will be cheaper and easier to administer than monoclonal antibodies — the only other presently available option for patients with mild-to-moderate COVID-19 at high risk for progression.

In a phase 1 clinical trial of healthy volunteers, molnupiravir was well tolerated and did not cause any serious adverse events, prompting a phase 2 trial to test it in patients with COVID-19. Molnupiravir was found to reduce infectious virus and speed up time to elimination of SARS-CoV-2 in outpatients with COVID-19. However, this study was not designed to evaluate clinical outcomes such as hospitalization and death.

Merck, the pharmaceutical company that developed the pill, recently reported results from a phase 3 randomized trial in a press release. They stated that molnupiravir was so effective in outpatients with COVID-19 that they stopped the trial early (i.e., it was unethical to continue giving patients the placebo). While we are unable to see the primary data and appraise the methods of the study, Merck stated that molnupiravir reduced the risk of hospitalization by about half for patients with mild-to-moderate COVID-19 with at least one risk factor for severe disease. Further, while eight patients in the placebo group died, no patients given molnupiravir died during the study period. These results are encouraging.

Merck submitted an approval request for molnupiravir to Health Canada under the Minister of Health's Interim Order on August 13, 2021. The review is ongoing. In the U.S., the FDA is scheduled to discuss whether molnupiravir should be granted emergency use authorization (EUA) on November 30.

Finally, molnupiravir is also being tested as post-exposure prophylaxis to evaluate whether it can stop the spread of COVID-19 within households. If it is effective at preventing severe disease in close contacts, it could be another tool to protect the most vulnerable, high-risk populations.

Original article published on EBSCO Health Notes. Written by:

  • Vito Iacoviello, MD, Deputy Editor for Infectious Disease, Allergy, and Immunology at DynaMed; and
  • Heather D. Marshall, PhD, Public Health Content Manager at DynaMed.

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About the author(s)

DynaMed is a clinician-focused tool designed to facilitate efficient and evidence-based patient care. Rigorous, daily review of medical literature by physician and specialist staff ensures timely and objective analysis, synthesis and guidance. DynaMed includes drug content from Micromedex, Canadian and international guidelines, and clinical images. CMA members have access to DynaMed, a point-of-care tool, included with their membership ― a tool valued at US$399 a year.