In late 2019, researchers at DRIVE were in the process of filing an investigational new drug (IND) application for EIDD-2801 for the treatment of influenza. But when the pandemic hit, human trials of the drug in influenza were put on hold and "all resources were directed toward COVID-19," Painter told MedPage Today by email.

DRIVE formed a partnership and transferred their IND to Ridgeback BioTherapeutics in January 2020. Ridgeback quickly started a phase I study that looked at pharmacokinetics, safety, and tolerability of EIDD-2801 in humans.

Within 9 weeks, results from the phase I study showed that the drug had "good oral bioavailability, was well tolerated, and had a good safety profile," Painter said at the press conference.

The phase I randomized double-blind controlled study included 130 healthy participants who were given different doses of molnupiravir or placebo. Results helped to establish dosage and showed that the drug was rapidly absorbed within less than 2 hours. Less than half of participants reported adverse events, and 93.3% of reported adverse events were mild. No serious adverse events were reported.

In partnership with Merck, Ridgeback next started a phase II trial, results of which were presented at the Conference on Retroviruses and Opportunistic Infections (CROI) in March 2021. The trial included 175 participants with confirmed COVID-19, including non-hospitalized individuals, who were randomized to twice daily molnupiravir or placebo.

At 5 days follow-up, no infectious virus could be grown from nose swabs taken from participants who received molnupiravir. In comparison, 24% of participants who received placebo still had infectious virus on nose swabs at day 5 (P=0.001).

"The hope is that the drug impacts transmission and early stage of disease, and lowers the burden on an already burdened healthcare system," Painter said during the press conference.

So far, animal studies seem to support the idea that molnupiravir could block transmission of the virus. A study in ferrets infected with SARS-CoV-2 has shown that treatment with molnupiravir stopped spread of the virus from infected animals to cage-mates.

"Like any direct-acting antiviral, molnupiravir will be more successful the earlier that it's given, to either eliminate the viral burden or significantly lower it to where clinical manifestations of disease and viral shedding are minimized. So that you both impact the need for advanced medical treatment and you arrest the spread of disease," Painter added.

Since presentation of the phase II results, Merck has announced that the phase III trial of molnupiravir will proceed in outpatients only. Based on interim analyses, Merck has said that "molnupiravir is unlikely to demonstrate a clinical benefit in hospitalized patients."

Following recommendations of an external data monitoring committee, the MOVe-OUT outpatient trial will focus on patients at high risk for severe illness and early treatment within 5 days of symptom onset, based on subgroup analysis suggesting potential benefit in these groups.

Merck has said that molnupiravir has gone through comprehensive safety studies, which have suggested that the compound does not induce mutations in mammalian cells.

In the development of molnupiravir, DRIVE also worked with collaborators at the Georgia Research Alliance Venture, Georgia State University, University of North Carolina at Chapel Hill, Vanderbilt University, Utah State University, and Colorado State University.

All funds for the post-licensing development of EIDD-2801/molnupiravir have been provided by Ridgeback Biotherapeutics and Merck. Emory University holds the patents and retains royalties to molnupiravir, according to Painter.