Ridgeback Biotherapeutics and Merck Announce Preliminary Findings from a Phase 2a Trial of Investigational COVID-19 Therapeutic Molnupiravir
Merck, known as MSD outside the United States and Canada, and Ridgeback Biotherapeutics, LP 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 today 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. These preliminary findings were presented today during Science SpotlightsTM at the 2021 Conference on Retroviruses and Opportunistic Infections (CROI 2021). Findings from the primary efficacy and safety endpoints and additional secondary objectives will be presented at an upcoming medical meeting.
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.
Today’s presentation described findings from the secondary endpoint of 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. At day 5, there was a reduction (nominal p=0.001, not controlled for multiplicity) in positive viral culture in subjects who received molnupiravir (all doses) compared to placebo: 0% (0/47) for molnupiravir and 24% (6/25) for placebo.
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.
“We are very pleased to share our initial Phase 2 infectivity data at this important conference, which remains at the forefront for critical clinical scientific information in infectious diseases,” shared Dr. Wendy Painter, Chief Medical Officer of Ridgeback Biotherapeutics. “At a time where there is unmet need for antiviral treatments against SARS-CoV-2, we are encouraged by these preliminary data.”
“The secondary objective findings in this study, of a quicker decrease in infectious virus among individuals with early COVID-19 treated with molnupiravir, are promising and if supported by additional studies, could have important public health implications, particularly as the SARS-CoV-2 virus continues to spread and evolve globally,” noted Dr. William Fischer, lead investigator of the EIDD-2801 2003 study and Associate Professor of Medicine, Division of Pulmonary Diseases and Critical Care Medicine at the University of North Carolina School of Medicine.
“We continue to make progress in our Phase 2/3 clinical programs evaluating molnupiravir in both outpatient and hospital settings and plan to provide updates when appropriate,” said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories.