Drugmaker Merck and its partner Ridgeback Biotherapeutics released data Friday showing their experimental pill to treat covid-19 is less effective than early clinical trials predicted, a finding that emerged as the Food and Drug Administration raised questions about the drug.
The study by the drugmakers found that, among participants receiving the pill, just one participant died during the trial, compared with nine deaths in the placebo group, the companies said in a news release Friday.
“It’s still a 30 percent effect, which is still good for a high-risk population,” said David Boulware, an infectious-disease physician and professor of medicine at the University of Minnesota Medical School who was not involved in Merck’s research. “It’s better than zero, and it’s a starting point, but it’s a little bit more modest.”
The FDA on Friday asked a panel of expert advisers to weigh the benefit of reduced hospitalizations and deaths in high-risk patients against potential risks associated with the drug. Because Merck and Ridgeback presented new clinical trial data to the agency after FDA scientists completed their review, regulators said their analysis may change ahead of a Tuesday meeting to consider the scientific evidence on the drug.
“The review issues and benefit/risk assessments may therefore differ from the original assessments provided in the briefing document which was based on the interim analysis,” an addendum to the FDA briefing materials said.
Merck and Ridgeback are seeking emergency-use authorization for their covid treatment, which would become the first easy-to-use pill to thwart the virus. The FDA advisory committee is expected to make a recommendation Tuesday, and agency officials typically follow the guidance of the advisers.
The agency reviewed data presented by the companies and determined that the clinical trial identified “no major safety concerns” related to adverse events. The most common side effects were mild-to-moderate diarrhea, nausea and dizziness. Still, the FDA identified several areas of concern, including potential risks for pregnant people and the possibility the drug could cause the coronavirus to mutate.
The FDA’s Antimicrobial Drugs Advisory Committee is scheduled to meet Tuesday to consider the scientific evidence on molnupiravir and weigh in on how the drug might safely be used to stave off severe infections.
The FDA could authorize the drug for use in treating patients at higher risk of hospitalization or death because of age or underlying health conditions such as obesity and heart disease. The agency’s review suggests that regulators may limit the drug’s use in people who are pregnant, hospitalized and vaccinated.
Merck’s pill works by interfering with an enzyme that the coronavirus needs to replicate itself and by changing the virus’s genome.
Unlike existing treatments — including monoclonal antibodies and the antiviral drug remdesivir — molnupiravir could be prescribed to patients and taken at home without a doctor’s direct supervision.
High-risk patients with covid-19 would start taking the pills within five days of developing symptoms and would continue using the drug twice a day for five days. The ease of use could make the treatment a powerful tool in preventing the worst outcomes by keeping mildly ill covid patients from getting worse and landing in the hospital.
While the drug could play a role in tamping down the toll of a pandemic that has killed more than 775,000 people in the United States, it is not a magic bullet. Some study participants, all of whom were unvaccinated and considered high-risk for serious infection, still ended up in the hospital with covid-related complications.
The FDA review suggests the pill will not be recommended for patients who are already sick enough to be hospitalized.
Because the medicine is not a perfect fix, experts have emphasized the continued need for people to get vaccinated to prevent serious covid infections.
The pill also carries potential risks, particularly for patients who are pregnant. Merck did not include in its clinical trial participants who were pregnant, and it required participants who could become pregnant to use birth control while taking the drug. That reflects concerns that the antiviral drug could disrupt the healthy development of a fetus because of the way it interferes with the virus’s genes.
The FDA proposed several ways to restrict the drug for pregnant patients because of the risk of birth defects and other potential problems.
“One approach is not to authorize [molnupiravir] for use during pregnancy because there are no clinical scenarios where the benefit outweighs the risk,” the agency’s review said.
A less restrictive approach would be to provide information about the risks and not recommend the pill during pregnancy, but allow doctors to prescribe the drug “at their discretion in certain clinical scenarios where the benefits were thought to outweigh the risks.”
Advisers to the FDA may also suggest precautions for women of childbearing age who take the drug, such as pregnancy tests and birth control.
Regulators also raised the question of whether vaccinated people should receive the pill. Because the vaccine offers robust protection against severe infection and death, the agency asked its advisers to evaluate whether vaccinated people would benefit sufficiently from the drug to justify the risks.
Merck’s pill was authorized for use in Britain this month for people older than 60 or with at least one risk factor for developing severe covid-19.
Regulators in the European Union gave member states the go-ahead to approve emergency use of the pill last week, as several countries in Europe contend with another wave of infections and enact new shutdown measures.
The FDA is expected to soon consider another antiviral pill — this one, Paxlovid, developed by Pfizer — after the company requested an emergency-use authorization last week. Pfizer’s drug, when taken within three days of symptoms, reduced the rate of death and hospitalization among high-risk patients by 89 percent, according to data from the company.