The Food and Drug Administration on Wednesday authorized the first pill for COVID-19, clearing for emergency use an antiviral treatment from Pfizer at a precarious moment in the two-year-old pandemic. One day later, on Thursday, the agency cleared a second pill developed by Merck & Co.
The drugs, Paxlovid from Pfizer and molnupiravir from Merck, represent valuable new tools for treating people with COVID-19, especially as the fast-spreading omicron variant appears to evade protection from past infections, most antibody medicines and, at least partially so, vaccines. Cases in the U.S. are rising quickly and places like New York City, Washington, D.C. and New Jersey are reporting record numbers of new infections.
Under the FDA's authorization, Paxlovid will be available for adults and children over 12 with mild or moderate cases of COVID-19 but who are at high risk of more severe symptoms. Molnupiravir's clearance, by contrast, is limited to adults over the age of 18 and comes with the important caveat that it should only be used to treat people for whom other options, like Paxlovid, aren't available or appropriate.
Clinical testing carried out by Pfizer and Merck showed both drugs could reduce the risk of hospitalization and death from COVID-19, dramatically so in the case of Paxlovid.
"As new variants of the virus continue to emerge, it is crucial to expand the country's arsenal of COVID-19 therapies using emergency use authorization, while continuing to generate additional data on their safety and effectiveness," said Patrizia Cavazzoni, head of the FDA office that approves most drugs, in a statement.
Initial supplies of both will be limited. Pfizer has contracted with the U.S. government to provide 10 million treatment courses in 2022, but only about 250,000 will be available through the end of January.
As pills to be taken at home, Paxlovid and molnupiravir are more convenient than antibody drugs developed by Regeneron, Eli Lilly and Vir Biotechnology, which are infused or injected by a healthcare professional. Regeneron and Lilly's medicines, which proved dramatically effective in preventing hospitalizations and deaths against early coronavirus strains, have appeared much weaker against omicron in laboratory testing. Vir's drug, by contrast, seems to hold up better.
Paxlovid won emergency authorization without the FDA convening a panel of outside advisers to review the drug, and just eight days after Pfizer released final data from its main clinical trial. Molnupiravir's OK, meanwhile, comes three weeks after a panel of outside FDA advisers narrowly supported the drug's use, with some on the committee citing concerns over the drug's potential safety risks and limited efficacy.
The FDA's authorization for molnupiravir reflected some of that hesitance, indicating the drug should be used as a secondary option when others are available. The regulator also advised against use of molnupiravir during pregnancy, citing the potential risk of birth defects. Men and women of childbearing age should use birth control when taking the drug and shortly afterwards, for the same reason.
Under the FDA's clearances, both drugs must be given within five days of symptoms beginning — typical for antiviral drugs that work by preventing viruses from replicating inside the body's cells.
Paxlvoid, which consists of a new drug called nirmatrelvir taken together with an older medicine called ritonavir, is taken twice a day for five days. Because it contains ritonavir, Paxlovid must be used carefully in patients with liver disease, the FDA said. The agency also advised against use with drugs that rely on certain enzymes that Paxlovid blocks or, conversely, boost production of those enzymes.
Molnupiravir's regimen consists of four pills taken every 12 hours for five days. Neither drug is meant to prevent infection, nor, the FDA warned, as a substitution for vaccination.
Paxlovid emerged from Pfizer's laboratories in a research sprint that spanned 16 months, a historically quick timeline for a new antiviral drug. Encouraging early data in early November was confirmed with full results from Pfizer's Phase 3 trial in mid-December, which showed treatment cut the risk of death or hospitalization in high-risk COVID-19 patients by 89% compared to a placebo.
Data also indicated a relatively benign profile for Paxlovid, with a similar percentage of trial volunteers experiencing a side effect after receiving the drug as those given placebo. There were fewer serious adverse reactions as well as fewer patients discontinuing treatment because of one.
Pfizer also tested Paxlovid in people who were vaccinated against COVID-19 or at lower risk of developing severe disease. Treatment did not meet the study's goal, failing to outperform placebo in curbing symptoms over four consecutive days, although it did reduce the risk of hospitalization for any cause by 70%.
Merck, which tried unsuccessfully to develop two coronavirus vaccines earlier in the pandemic, got to work early on a COVID-19 antiviral. The company licensed molnupiravir in May 2020 from private biotech Ridgeback Biotherapeutics, which had acquired rights from Emory University several months earlier. Emory developed the drug as a broad-spectrum antiviral, initially testing it against the coronaviruses that cause SARS and MERS.
Molnupiravir's path to authorization looked clear two months ago, when Merck and Ridgeback reported Oct. 1 that the drug reduced hospitalization and death from COVID-19 by roughly 50% versus placebo. The study results, calculated at an interim analysis before all participants could be evaluated, were so persuasive that independent trial monitors told Merck to stop testing and ask for FDA authorization.
But results from patients evaluated afterwards made molnupiravir appear much less effective, although the interim analysis is considered the only formal statistical review of the trial. When all trial participants were assessed, data from Merck later showed, the reduction in risk of hospitalization and death was estimated to be only about 30%.
The seeming decline in efficacy was one reason some outside experts on the FDA's panel voted against recommending authorization. Others were worried about the way the drug works and whether it might result in new, more troublesome coronavirus variants.
The drugs' authorizations will set in motion distribution by the federal government of tens of millions of pills it bought in advance from Pfizer and Merck. The U.S. spent more than $5 billion to preorder 10 million treatment courses of Paxlovid, and about $2.2 billion to secure over 3 million courses of molnupiravir.
Initial shipments of 65,000 courses of Paxlovid are set to go out by the end of December, according to the Health and Human Services Department. Pfizer anticipates it can make 120 million courses of Paxlovid in 2022, up from an initial projection of 50 million that was later revised to 80 million.
Note: This story has been updated with additional detail from the FDA's authorization and on Pfizer's supply expectations.