The Food and Drug Administration on Thursday granted emergency authorization to Merck’s molnupiravir, an antiviral pill shown to reduce hospitalization and death in cases of Covid-19, but only in cases where other FDA-authorized Covid treatments are not accessible or clinically appropriate.
The approval comes a day after the FDA authorized an antiviral pill from Pfizer for much broader use in patients as young as 12.
“Today’s authorization provides an additional treatment option against the COVID-19 virus in the form of a pill that can be taken orally. Molnupiravir is limited to situations where other FDA-authorized treatments for COVID-19 are inaccessible or are not clinically appropriate and will be a useful treatment option for some patients with COVID-19 at high risk of hospitalization or death,” Patrizia Cavazzoni, director of the FDA’s Center for Drug Evaluation and Research, said in a statement.
A Merck spokesperson said Merck is ready to ship hundreds of thousands of courses of treatment within days of authorization and 1 million courses over the next few weeks in the U.S. Ten million courses are ready to be packaged and distributed worldwide.
In clearing molnupiravir, developed by Merck and Ridgeback Therapeutics, the FDA accepted a narrow recommendation from a panel of advisers who were torn over whether to back the therapy. In a clinical trial, a five-day course of the pill was shown to be only modestly effective. The data also showed it could cause birth defects if used in pregnancy.
Acknowledging those risks, the FDA included a number of warnings and precautions with its authorization. The drug is not recommended for use in pregnancy, but doctors can prescribe it to pregnant women at their discretion. Females of childbearing age should be using contraception during treatment and for four days after the final dose. Males of childbearing age are also advised to use contraception during treatment and for three months following their last dose. While Pfizer’s Paxlovid was authorized for children as young as 12, molnupiravir is not being authorized for patients younger than 18. Some data from animals indicate the drug might affect bone and cartilage growth.
Antivirals are seen as potentially critical weapons in the fight against Covid-19, buttressing but by no means replacing tools like vaccines and monoclonal antibodies. Ideally, oral treatments would be easy to access for patients who contract the SARS-CoV-2 virus and prevent hospitalization or death. The need has increased with the new Omicron variant, because many of the monoclonal antibodies against Covid appear to be less potent against it, while the oral antivirals appear to maintain their efficacy.
But data on molnupiravir showed its potential could be limited. Initial results from a study showed it reduced hospitalizations by 50% — but that figure was revised downward to 30% after full data were released. In the 1,433-patient study, fewer patients died when they received the treatment. There were nine deaths in the placebo group in the final analysis, and one in the molnupiravir group.
Patients in the study had mild-to-moderate Covid-19 and had at least one risk factor associated with poor disease outcomes, including being over 65, being overweight, or having cardiovascular disease.
Dean Li, Merck’s head of research and development, emphasized in an interview that in that study, molnupiravir reduced the number of deaths. There were nine in the group that received placebo and one in the molnupiravir group.
“There’s a 90% reduction in death,” Li said. “And I would just emphasize that as people think through are you going to prescribe this medicine.” He pointed to molnupiravir’s lack of interactions with other drugs and the lack of a need to reduce dose for those with kidney impairment or exercise caution in those with liver impairment, both steps recommended for Paxlovid. “I think this is a really important contribution,” Li said.
Pfizer’s Paxlovid appears to have advantages in both efficacy and safety, but molnupiravir is likely to still have a role. At the beginning of 2022, there will be a much greater supply of molnupiravir. Pfizer has said it will produce greater than 180,000 courses by the end of the year, and then will make 140 million courses in 2022.
Another concern raised at the advisory committee for molnupiravir was that the drug might lead to new variants of SARS-CoV-2 because of its mechanism of action.
“With all respect, I think it’s incumbent upon you to make some effort to make an estimate of what is the likelihood of escape mutants occurring as a result of your drug,” said James Hildreth, a panelist and the CEO of Meharry Medical College.
“In our hands, the cell culture, resistance and selection studies, there is an extremely high barrier to resistance,” Li said.
One approach that’s been suggested to combat resistance would be to combine the medicines.
“I think they’re very effective and one could argue not to mix them immediately, but that’s something that might need to be thought through in the future,” Li said.