The oral antiviral molnupiravir cuts the risk of hospitalization and death from COVID-19 by 50% in people who have mild to moderate forms of the disease. Merck & Co. and Ridgeback Biotherapeutics reported the data, which come from interim analysis of their Phase 3 trial, in a press release. The data have not been peer reviewed.
Based on the positive results, Merck plans to submit an application for Emergency Use Authorization (EUA) to the US Food and Drug Administration as soon as possible, and seek similar approval from other regulatory agencies worldwide.
The companies report that 28 of 385 patients—about 7%—who received molnupiravir were hospitalized with COVID-19. No patients died. In the group that received a placebo, 53 of 377 patients—14%—were hospitalized, and 8 of them died.
In addition to a positive diagnosis of COVID-19, all of the patients in the trial had at least one risk factor associated with poor disease outcomes, such as obesity or being age 60 or older. The companies also report that molnupiravir was equally effective at treating the Gamma, Delta, and Mu variants of the disease as the original strain.
Furthermore, the study indicated that the drug is safe: reports of adverse events and adverse event–related discontinuation of the therapy in the molnupiravir group were either similar to or lower than those in the placebo group.
Molnupiravir “is the first oral antiviral to have shown efficacy in the outpatient setting for COVID,” said Daria Hazuda, Merck’s vice president for infectious disease and vaccine discovery, during a briefing for reporters. Although Gilead Sciences’ Veklury (remdesivir) is also an antiviral approved for treating COVID-19, that drug must be given via infusion in a hospital, which has limited its use.
Sina Bavari, an expert in antiviral therapies and founder of Edge BioInnovation Consulting and Management, says in an email that “having an oral antiviral will have a big impact on the pandemic. The modality will add an additional layer of defense, which can be given in outpatient settings.”
Andy Mehle, a virologist at the University of Wisconsin–Madison, says that Merck and Ridgeback “put themselves behind the eight ball” by looking at patients who had additional risk factors and were also symptomatic. “And the fact that the compound still worked, and reduced hospitalization by 50%—that, to me, is very surprising and encouraging.” Mehle says he’d like to see if molnupiravir prophylactically prevents infection in people who have been exposed to SARS-CoV-2, the virus that causes COVID-19, and if the compound prevents infected people from transmitting the virus.
Scientists at the Emory Institute for Drug Development and Drug Innovation Ventures at Emory University invented molnupiravir, which they called EIDD-2801, several years ago as a treatment for Venezuelan equine encephalitis virus. Their research showed the molecule was also effective at treating other viruses, including influenza, in cells and in animals.
The active form of molnupiravir works by interfering with a virus’s RNA-dependent RNA polymerase. It can exist in two forms via tautomerization. In one form, it mimics cytidine, and in the other form, it mimics uridine. Switching between these two forms causes mismatches during viral transcription, which ultimately leads to mutations in the viral genome and copies of the virus that can’t function.
Patrick Fier, the Merck chemist who led the scale up of molnupiravir, said during C&EN’s Talented 12 webinar on Sept. 28 that the company has already made 75,000 kg of the antiviral, enough to supply roughly 9 million patients.
“We also entered into licensing agreements with a number of low-cost manufacturers to make the drug available to lower-income countries,” Hazuda said.
Daina M. Graybosch, a stock analyst with SVB Leerink, said in a note to investors that molnupiravir, if authorized, could bring in nearly $10 billion in near-term orders. “Although the magnitude of risk reduction with molnupiravir does not reach levels achievable with antibody treatment (70%-85%), a pill has inherent logistical and cost advantages which could make molnupiravir the preferred treatment for COVID-19 around the world,” Graybosch said.