FDA authorizes Mercks anti-coronavirus pill, a second treatment option

Doctors have clamored for easy-to-use medications throughout the pandemic, but the new drug, molnupiravir, has had an uneven reception because of its modest efficacy and potential safety risks. Some experts say another tool will be helpful as the omicron variant, which is resistant to other key treatments, surges. But others say they would be hesitant to use the drug.

The Food and Drug Administration authorized the five-day course of treatment in patients 18 and older who are at high risk of severe covid-19 and "for whom alternative COVID-19 treatment options authorized by the FDA are not accessible or clinically appropriate."

That is a limitation that will leave physicians deciding how to prioritize an array of treatments among patients at risk of severe covid-19. But those treatment decisions are set against a backdrop of supply shortages.

One monoclonal antibody treatment remains effective against omicron but is in short supply and has to be given by an intravenous infusion. Doses of a Pfizer antiviral pill authorized this week are expected to be limited in the near-term and the drug isn't appropriate for everyone. A study published Wednesday showed that a three-day course of intravenous remdesivir, currently approved for hospitalized patients, could be effective in keeping people with milder cases out of the hospital.

"This week's actions are important steps in the fight against covid-19 and demonstrate the agency's commitment to expanding the arsenal of treatment options available to help the public," Patrizia Cavazzoni, director of the FDA's Center for Drug Evaluation and Research, said at a news briefing.

Molnupiravir, developed by Merck and Ridgeback Biotherapeutics, cut the risk of hospitalization and death in high-risk patients by 30% when given within five days of symptom onset. In contrast, Pfizer's antiviral drug, authorized a day earlier, reduced hospitalizations and death by 88% when given with five days.

Molnupiravir works by introducing mutations to the virus, a different mechanism than Pfizer's pill, which interferes with a protease the virus needs to make copies of itself.

Dean Y. Li, president of Merck Research Laboratories, said the advantages of the drug include that clinicians will not have to worry about interactions with commonly prescribed medications or worry about patients' liver and kidney function. Pfizer's antiviral Paxlovid interacts with many commonly used drugs and is not recommended for people with severe liver and kidney problems.

"It's an important part of the armamentarium, and we do think multiple mechanisms of action are going to be important," Li said.

Because of the way the Merck drug works, some experts fear it will fuel the rise of new variants or could cause mutations in people who take it - despite various tests that gave FDA reviewers confidence those risks were low overall.

Molnupiravir is not recommended for use during pregnancy. Men and women of childbearing potential are recommended to use birth control, with men recommended to use birth control for three months after the last dose. It is authorized for people 18 and older because it can affect bone and cartilage growth.

"While 30 percent is definitely less than 88 percent [for Pfizer], this is still better than 0 percent," said David Boulware, an infectious-diseases physician at the University of Minnesota Medical School. "Due to safety concerns, pregnant women as well as men or women who are trying to conceive should not receive molnupiravir."

Other experts questioned the modest benefit and worried that it could lead to the emergence of future variants, despite the fact that FDA reviewers found those risks to be low. A committee of external advisers reviewed the drug in November, and were divided on whether to recommend authorization of the pill. Even some advisers who voted to recommend authorization said the drug would not be their first choice.

"Someone taking that drug is cheating themselves out of the opportunity to take a better, more effective drug," said Michael Z. Lin, a biochemist at Stanford Medicine who has been working on a different type of antiviral drug. "Approval of Merck's drug would be the worst decision in FDA history. . . . It's almost certainly going to create viral variants that escape."

John Farley, director of the Office of Infectious Diseases at FDA, called it a "challenging" risk-benefit consideration.

He said the virus also mutates in untreated people during the course of an infection. Mutations in the virus were "a bit more frequent" in people who were treated with molnupiravir, and the agency plans to continue to monitor the risk.

Farley said there were other factors that influenced the agency's conclusion that benefits of the drug outweighed the theoretical risk it could generate a worrisome new variant. The drug causes the amount of virus in people's body to plummet, and patients would be isolating until they recover.

Molnupiravir has been authorized in the United Kingdom, but France canceled its order for the drug this week.

Molnupiravir may be the most plentiful option as cases soar, driven by the omicron variant. The federal government dispatched 65,000 treatment courses of Pfizer's antiviral Paxlovid in its first shipment this week. Merck will deliver "several hundred thousand" treatment courses in the next couple of days, and up to 1 million doses in the next two weeks, said John McGrath, Merck's senior vice president of external manufacturing and strategy.

Jeffrey Zients, the White House coronavirus response coordinator, said that by the end of January, the government expects to ship 3 million treatment courses to the states. Pfizer's production is expected to ramp up more slowly.

The federal government will allocate doses to states, which will then decide how the pills should be distributed and prioritized, said Tom Kraus, vice president of government relations at the American Society of Health-System Pharmacists.

Kraus noted that consumer and physician preference played a role in vaccine uptake, and he expected that patients would have a preference for one drug. But, as with the initial vaccine rollout, demand will likely outstrip supply, causing shortages and a lack of choices.

"At the end of the day, omicron is racing across the country. It seems like the federal government needs to be doing everything they can do to rapidly bring supply online," Kraus said. "The existence of these drugs is unequivocally a reason to be positive. It is absolutely another substantial arrow in the quiver, to fight this pandemic."