Denpa News In the spring of 2020, scientists around the world tossed everything in their freezers into Petri dishes, along with human cells and SARS-CoV-2, the virus that causes COVID-19. The goal was to find agents that could protect cells from this new virus, and many drugs were found to be effective in these in vitro experiments – including hydroxychloroquine, ivermectin, and some antivirals against HIV. But protecting cells in a petri dish usually does not guarantee clinical efficacy in patients. Many of the promising drugs tested in vitro have failed or shown inconclusive results in clinical trials, and some are still in the research phase.
One drug that has been shown to be effective in recovering COVID-19 patients is an antiviral drug called remdesivir. First described in 2016, remdesivir was shown to be a promising drug against Ebola, MERS-CoV and SARS-CoV-1 in laboratory studies, and then it was found to be able to withstand SARS-CoV-2 as well. COVID-19 was the first indication for remdesivir to be approved by the US Food and Drug Administration (FDA) in October 2020. However, remdesivir is only recommended for the treatment of patients hospitalized with severe COVID-19. Thus, for patients with mild to moderate COVID-19 disease, only intravenous monoclonal antibodies remain as a treatment option.
The newest drug to enter the drug race against COVID-19 is another antiviral drug, molnupiravir. Molnupiravir is similar in principle to remdesivir. Both drugs inhibit viral RNA polymerase, thereby blocking the virus’s ability to replicate itself. The drug was originally investigated for the treatment of influenza, but at the onset of the pandemic it was tested against SARS-CoV-2 and, like remdesivir, has been shown to inhibit the development of SARS-CoV-2 in vitro.
In a phase 1 clinical trial in healthy volunteers, molnupiravir was well tolerated and did not cause any serious side effects, prompting a phase 2 trial in patients with COVID-19. Molnupiravir has been found to reduce viral infection and accelerate the elimination time of SARS-CoV-2 in outpatients with COVID-19. However, this study was not intended to assess clinical outcomes such as hospitalization and death.
Merck recently issued a press release on the results of a Phase 3 randomized trial , suggesting that molnupiravir was so effective in COVID-19 patients in an outpatient setting that they stopped the study early (i.e. it was unethical to continue giving placebo to patients.) While we are unable to review the primary data and evaluate the study methods, Merck claims that molnupiravir reduced the risk of hospitalization by about half for patients with mild to moderate COVID-19 who have at least one risk factor for severe disease. In addition, while eight patients in the placebo group died, none of the patients treated with molnupiravir died during the study period. On November 30, the US Food and Drug Administration (FDA) is scheduled to discuss whether molnupiravir should be granted permission to be approved for emergency use.
These results are encouraging. Molnupiravir is an oral tablet taken twice daily for five days that is cheaper and easier to administer than monoclonal antibody therapy – the only option currently available for patients with mild to moderate COVID-19 with high risk of developing a severe form.
Finally, molnupiravir is also being tested as a PEP to assess whether it can stop the spread of COVID-19 in the home. If it proves to be effective in preventing severe disease at close contacts, it could be another tool for protecting the most vulnerable populations at high risk.