The New York Times, November 30, 2021 (with Rebecca Robbins)
A federal advisory committee on Tuesday voted to recommend that the government for the first time authorize the use of an antiviral pill to combat the worst effects of Covid-19.
The advisory committee, in a surprisingly narrow 13-to-10 vote, endorsed the pill from Merck, while public health officials worldwide raced to buttress their defenses against the newly emerging Omicron variant of the coronavirus.
The Merck treatment, known as molnupiravir, has been shown to modestly reduce the risk of hospitalization and death from Covid. The pill could be authorized for use in the United States within days and available to patients within weeks.
In the coming weeks, the F.D.A. may also authorize a similar pill from Pfizer that appears to be significantly more effective than Merck’s. Together, the arrival of the two easy-to-use treatments could provide a cushion against a resurgent virus.
The F.D.A. advisory panel, a group of experts on antimicrobial drugs, recommended that Merck’s treatment be authorized for people with Covid who are at high risk of becoming severely ill. That would most likely cover tens of millions of Americans who are older or have medical conditions such as obesity, diabetes or heart disease.
But the committee’s close vote reflected doubts about the pill’s effectiveness and concerns that it could cause reproductive harm.
“The efficacy of this product is not overwhelmingly good,” said Dr. David Hardy, an infectious disease physician in Los Angeles. Still, he voted to recommend the drug, saying “there is a need for something like this.”
Other members of the committee who voted against authorization said more research was needed about the drug’s safety. “The risk of widespread effects on potential birth defects, especially delayed effects on the male, has not been adequately studied,” said Dr. Sankar Swaminathan, an infectious disease specialist at the University of Utah.
The pills, which doctors will prescribe and will be dispensed at pharmacies, are much more convenient and are expected to reach many more people than the monoclonal antibody treatments that have typically been used to aid high-risk Covid patients. The antibody treatments are expensive and typically given intravenously at hospitals or clinics.
The Biden administration has been hoping that the emergence of the antiviral pills from Merck and Pfizer will help end the most acute phase of the pandemic. The U.S. government has spent billions of dollars to secure millions of treatment courses of the new pills.
Merck’s clinical trials primarily enrolled people who were infected with the Delta, Mu and Gamma variants of the coronavirus. Scientists have yet to run experiments to see how well the pills block Omicron viruses from replicating. But there are reasons to think they would remain effective even if the variant can sometimes evade vaccines, as well as monoclonal antibodies.
Omicron has more than 30 mutations on the so-called spike protein that latches on to human cells. Some of those mutations may make it hard for vaccine-produced antibodies to attack the virus.
But the pills do not target the spike protein. Instead, they weaken two proteins involved in the virus’s replication machinery. Omicron carries only one mutation in each of those proteins, and neither looks as if it would stop the pills from doing their jobs.
A Merck executive, Dr. Nicholas Kartsonis, told the advisory panel on Tuesday that the company was “feverishly working” to collect samples from people infected with the Omicron variant that it can use in laboratory studies to help determine whether the drug will work against the variant.
“We expect based on what we know about the Omicron variant that molnupiravir would be effective,” he said.
Even before the expected arrival of Omicron, coronavirus cases are rising in many regions of the United States, notably the Upper Midwest and Northeast. The sharp increase has raised fears about a winter surge fueled not only by the new variant but also by indoor holiday gatherings and the refusal of tens of millions of Americans to be vaccinated.
In a clinical trial, molnupiravir was found to reduce by 30 percent the risk of hospitalization or death when given to high-risk, unvaccinated volunteers within five days after they started showing symptoms. It appears to be substantially less effective than Pfizer’s pill, which was found to reduce that risk by 89 percent. Monoclonal antibody treatments have been found to reduce the risk of hospitalization or death by at least 70 percent.
Assuming the F.D.A. authorizes the use of molnupiravir, supplies are likely to be limited at first.
In addition, the compressed time frame of getting the pills could pose a challenge. Merck’s treatment is supposed to be given within five days of the start of symptoms and is taken as 40 pills over five days.
Patients will most likely need to test positive for the coronavirus and see a physician, who will write a prescription for a pack of pills that can be picked up at a pharmacy. But it often takes days to get results from a PCR test, and in some parts of the country it is hard to find tests that return results within 15 minutes. In addition, many people don’t have regular doctors to turn to for prescriptions.
The Biden administration has ordered enough courses of Merck’s treatment, at about $700 per person, for 3.1 million people. Merck is expected to supply those pills before February. By contrast, Pfizer is expected to supply only enough of its pills to cover 300,000 people in the United States before the end of February.
One question hanging over the treatment is how many eligible Americans will refuse to take the new pills. In a Morning Consult poll released this week, about half of unvaccinated adults — the primary group expected to need the pills — said they would not take F.D.A.-authorized antiviral pills if they got sick with Covid.
A number of committee members raised questions about the safety of the pill. The treatment works by inserting errors into the virus’s genes. Some scientists say there is a theoretical risk that it could trigger mutations in cells as well, potentially causing reproductive harm or a long-term risk of cancer.
“The overall risk of mutagenicity in humans is considered low,” Dr. Aimee Hodowanec, a senior medical officer at the F.D.A., said at the meeting, referring to the potential for the drug to induce mutations in the DNA of people taking it.
Merck says its laboratory tests and clinical trial data indicate that the drug is safe and does not cause worrisome mutations in humans.
Members of the F.D.A. panel said the pills generally should not be given to pregnant women.
Merck executives said on Tuesday that the company would begin a program to track any women who take molnupiravir while pregnant.
Britain, which authorized Merck’s pill in early November, recommended that it not be given to pregnant or breastfeeding women and that women who could become pregnant use contraception while taking the drug and for four days after.
Copyright 2021 The New York Times Company. Reprinted with permission.