On Mar. 5, 2021, Merck and Ridgeback Biotherapeutics, announced preliminary results from Ridgeback’s Phase 2a randomized, double-blind, placebo-controlled trial to evaluate the safety, tolerability, and efficacy to eliminate SARS-CoV-2 viral RNA of molnupiravir (EIDD-2801/MK-4482), an investigational oral antiviral agent.

The companies reported findings on one secondary objective from the Phase 2a study, showing a reduction in time (days) to negativity of infectious virus isolation in nasopharyngeal swabs from participants with symptomatic SARS-CoV-2 infection, as determined by isolation in Vero cell line culture.

This multi-center U.S. Phase 2a study enrolled 202 non-hospitalized adults who had signs or symptoms of COVID-19 within 7 days and confirmed active SARS-CoV-2 infection. The primary efficacy objective was reduction in time to viral negativity measured by reverse transcriptase polymerase chain reaction (RT-PCR) analysis of nasopharyngeal swabs. Periodic samples were collected for virologic analysis. Of the 182 participants with an evaluable nasopharyngeal swab, 42% (78/182) showed detectable levels of cultured virus at baseline. The full study results remain blinded and will be shared at a later date, as they become available. Other Phase 2 and Phase 2/3 studies are underway.

Of 202 treated participants, no safety signals have been identified and of the 4 serious adverse events reported, none were considered to be study drug related. In addition to the ongoing clinical studies, Merck has conducted a comprehensive nonclinical program to characterize the safety profile of molnupiravir. This program included assays such as Big Blue and PIG-a designed to provide a robust measure of a drug or chemical’s ability to induce mutations in vivo. Animals were administered molnupiravir for longer and at higher doses (mg/Kg) than those employed in human studies.

The totality of the data from these studies indicates that molnupiravir is not mutagenic or genotoxic in in vivo mammalian systems. lts who had signs or symptoms of COVID-19 within 7 days and confirmed active SARS-CoV-2 infection. The primary efficacy objective was reduction in time to viral negativity measured by reverse transcriptase polymerase chain reaction (RT-PCR) analysis of nasopharyngeal swabs. Periodic samples were collected for virologic analysis. Of the 182 participants with an evaluable nasopharyngeal swab, 42% (78/182) showed detectable levels of cultured virus at baseline. The full study results remain blinded and will be shared at a later date, as they become available. Other Phase 2 and Phase 2/3 studies are underway.