The findings reported on a secondary objective to reduce time to negative test result of infectious SARS-CoV-2 virus in individuals with symptomatic COVID-19. UNC School of Medicine’s William Fischer, MD, is the lead investigator on the study of Molnupiravir, the investigational drug also known as EIDD-2801.
Merck and Ridgeback Biotherapeutics announced preliminary results from Ridgeback’s Phase 2a randomized, double-blinded, 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. Findings from the primary efficacy and safety endpoints and additional secondary objectives will be presented at an upcoming medical meeting.
“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,” said William Fischer, MD, lead investigator of the EIDD-2801 2003 study and associate professor in the UNC Division of Pulmonary Diseases and Critical Care Medicine at the University of North Carolina School of Medicine.
Earlier this year, UNC School of Medicine researchers led by Victor Garcia, PhD, released news of EIDD-2801 being very effective at eradicating and preventing SARS-CoV-2 from specialized animal models of COVID-19.
This multi-center U.S. Phase 2a study enrolled 202 non-hospitalized adults who had signs or symptoms of COVID-19 within seven 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.
This week’s data describe 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 five, 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.
Molnupiravir (EIDD-2801/MK-4482) is an investigational, orally-bioavailable form of a potent ribonucleoside analog that inhibits the replication of multiple RNA viruses including SARS-CoV-2, the causative agent of COVID-19. Molnupiravir has been shown to be active in several models of SARS-CoV-2, including for prophylaxis, treatment, and prevention of transmission, as well as SARS-CoV-1 and MERS. EIDD-2801 was invented at Drug Innovations at Emory (DRIVE), LLC, a not-for-profit biotechnology company wholly owned by Emory University. Since licensed by Ridgeback all funds used for the development of EIDD-2801 by Ridgeback have been provided by Wayne and Wendy Holman and Merck.