FDA Authorizes Merck’s Covid-19 Pill for At-Home Treatment

The FDA recommended using the Merck drug only if other authorized drugs aren’t available and medically appropriate. Health experts have raised safety concerns about the Merck drug, which also was less effective in testing than an antiviral from Pfizer Inc. On Wednesday, the FDA cleared the Pfizer pill, Paxlovid, also for people to take at home to try to stay out of the hospital.

Merck’s drug was found to be 30% effective in reducing the risk of hospitalization and death in a key study, while Pfizer said Paxlovid was 89% effective at reducing risk of hospitalization and death in a key study. Both drugs were tested before the Omicron variant emerged.

The addition of the pills may bolster the fight against Omicron as it hurtles around the U.S. Researchers have said they expect the drugs to work against the new strain, though they are waiting for study results.

Molnupiravir “will be a useful treatment option for some patients with Covid-19 at high risk of hospitalization or death,” said Dr. Patrizia Cavazzoni, director of the FDA’s drugs division.

Merck research chief

Dean Li

said that molnupiravir reduced the risk of death by 90% in the company’s clinical trials. “That’s a really important number for physicians to keep in mind,” he said in an interview.

With a molnupiravir prescription, adults would take eight pills daily for five days, starting within five days of showing symptoms. The FDA didn’t authorize use among people who are hospitalized or under the age of 18.

The drug is expected to be available in the coming days in pharmacies, doctors’ offices and other locations. Initial supplies will be limited, though Merck says it is ramping up manufacturing.

Within the U.S., Merck will ship several hundred thousand treatment courses in the several days, nearly a million courses over the next couple of weeks, and up to three million by the end of January, John McGrath, who leads Merck’s molnupiravir manufacturing operations, said in an interview.

The U.S. treatment courses have been purchased by the federal government, which will allocate them to states, said Mr. McGrath.

Citing the strong results for Pfizer’s drug, Wall Street analysts have scaled back sales estimates for molnupiravir and said they expect demand for the drug to be limited. Analysts expect Merck’s drug won’t sell nearly as much as Pfizer’s.

Until the FDA’s recent moves, there hadn’t been an antiviral like Paxlovid or molnupiravir cleared to reduce the risk of hospitalization in adults with the virus. Another kind of therapy, known as an antibody drug, has been in use to prevent severe disease.

Yet the antibody treatments are expensive to administer, can be tough to find in rural areas and are primarily administered at physician clinics or hospitals and given via injections or infusions.

Given the drawbacks, doctors and health authorities have been looking for a pill that people could easily take at home to try to avoid hospitalization.

Also, several of the antibody drugs don’t appear to work well against Omicron, prompting some hospitals to halt their use given the variant’s spread.

Anticipation for molnupiravir grew when the companies reported that a preliminary analysis of study results found the drug 50% effective. Yet the excitement was tempered after a final analysis found the drug efficacy was lower.

Some health experts have also raised safety concerns and whether molnupiravir might cause mutations in cells that are harmful to people. Merck and Ridgeback have said the drug is safe, and testing in humans found it didn’t cause mutations.

The FDA has said its own review of the companies’ data found no major safety concerns in late-stage testing. The FDA also found the treatment presented a low risk of mutation, known as mutagenicity.

But the FDA’s authorization of molnupiravir was for a more limited set of people than Paxlovid’s, which was cleared for use in people 12 years and older who aren’t taking a drug that could react to the treatment regimen.

The FDA recommended against prescribing molnupiravir to anyone pregnant unless the benefits outweigh the risks because testing in animals indicated the drug could cause fetal harm.

Molnupiravir is an option for patients who shouldn’t take Paxlovid because one of the components of Paxlovid can have negative interactions with certain non-Covid medications that patients are taking, FDA officials said.

How Molnupiravir Works

The drug interferes with SARS-CoV-2’s ability to reproduce within a patient’s cells.

How molnupiravir interferes with RNA replication

How viral reproduction works

New RNA is assembled by stringing together blocks of chemical units called bases.

1. The virus infiltrates a patient’s cells.

The shape of the molnupiravir molecule resembles one of these bases. When the drug enters an infected cell, it is incorporated into the growing viral RNA strand.

2. It begins making copies of its RNA, which contains the genetic instructions for building new viruses.

This intrusion introduces errors into the virus’s genetic code, rendering the virus unable to make viable copies of itself.

3. Once an RNA molecule is complete, it gets packaged into a new viral coating and exported from the cell. These new copies go on to infect more cells.

How viral reproduction works

The virus infiltrates a patient’s cells.

It begins making copies of its RNA, which contains the genetic instructions for building new viruses.

Once an RNA molecule is complete, it gets packaged into a new viral coating and exported from the cell. These new copies go on to infect more cells.

How molnupiravir interferes with RNA replication

New RNA is assembled by stringing together blocks of chemical units called bases.

The shape of the molnupiravir molecule resembles one of these bases. When the drug enters an infected cell, it is incorporated into the growing viral RNA strand.

This intrusion introduces errors into the virus’s genetic code, rendering the virus unable to make viable copies of itself.

How viral reproduction works

The virus infiltrates a patient’s cells.

It begins making copies of its RNA, which contains the genetic instructions for building new viruses.

Once an RNA molecule is complete, it gets packaged into a new viral coating and exported from the cell. These new copies go on to infect more cells.

How molnupiravir interferes with RNA replication

New RNA is assembled by stringing together blocks of chemical units called bases.

The shape of the molnupiravir molecule resembles one of these bases. When the drug enters an infected cell, it is incorporated into the growing viral RNA strand.

This intrusion introduces errors into the virus’s genetic code, rendering the virus unable to make viable copies of itself.

“This was a challenging benefit-risk consideration,” John Farley, director of the FDA’s Office of Infectious Diseases, said about the agency’s review of Merck’s drug.

Another issue with molnupiravir, FDA officials said, is the potential risk that it could lead to variants of the virus developing in patients taking the drug, which might then escape and be transmitted to others. But FDA officials said the drug reduces viral loads, and patients should be isolating while undergoing treatment, which could mitigate this potential risk.

Molnupiravir targets a different part of the virus than the spike protein that vaccines and other treatments focus on. The drug targets machinery the virus uses to replicate, rather than the spike protein, the structure that helps the virus infiltrate cells. Pfizer’s Paxlovid doesn’t target the spike protein either and works differently than other Covid-19 vaccines and drugs.

Merck has said it plans to study whether molnupiravir is effective against the variant but it has presented data showing how the drug is effective against other variants and expects similar results with Omicron.

Omicron has several mutations to the spike protein, which researchers say could help the variant evade vaccines and drugs trained on that part of the virus.

Merck, based in Kenilworth, N.J., has agreed to provide the U.S. government with 3.1 million courses of the drug for about $2.2 billion.

In November, an outside panel of scientific advisers to the FDA narrowly recommended the agency authorize molnupiravir.

Panel members who voted against the recommendation said they were concerned with how there wasn’t a clear explanation on why molnupiravir’s efficacy changed and that the drug’s benefit to patients may be minimal.

Some also said they were concerned the drug could cause mutations in human cells and that more study of the drug is needed to assess that possibility.

The U.K. cleared molnupiravir for use in November.

To try to make molnupiravir more readily available to people in low- and middle-income countries, Merck has licensed out the drug to the United Nations-backed Medicines Patent Pool and generic drugmakers.

Despite such efforts, some drug-access advocates and public-health experts say that molnupiravir and Pfizer’s antiviral are likely to take longer to reach poorer countries because of manufacturing and pricing obstacles.

—Joseph Walker contributed to this article.

Write to Jared S. Hopkins at jared.hopkins@wsj.com and Betsy McKay at betsy.mckay+1@wsj.com