The New York Times, March 16, 2023 (with Christina Jewett)
A panel of expert advisers to the Food and Drug Administration on Thursday endorsed Paxlovid as a treatment for adults with Covid who are at high risk for progression to severe illness. The move is likely to lead to full approval of the drug, which has been available under emergency use authorization.
The 16-1 vote came after the agency released a new analysis showing that Paxlovid reduced hospitalizations and deaths among both unvaccinated and vaccinated people. Agency researchers estimated, based on Covid rates in January, that Paxlovid could “lead to 1,500 lives saved and 13,000 hospitalizations averted each week in the United States.”
“I’d say, besides oxygen, Paxlovid has probably been the single most important treatment tool in this epidemic and continues to be,” Dr. Richard A. Murphy, chief of infectious diseases at Veterans Affairs White River Junction Medical Center in Vermont, said explaining his vote in favor of the treatment.
Consumers have been particularly concerned about reports that people who take the drug experience a “rebound” of Covid, in which symptoms return a few days after disappearing. The F.D.A.’s analysis did find evidence of rebound among patients receiving the treatment, but the data also showed that some Covid patients who did not receive Paxlovid experienced rebound as well.
The agency concluded that there was not a significant difference in rebound rates between the two groups and that rebound had no impact on the risk of developing severe illness. At Thursday’s meeting of experts, Dr. Stephanie Troy, an F.D.A. researcher, suggested that Covid rebound “may be a natural part of Covid-19 clinical course in a small subset of patients,” whether or not they take Paxlovid.
Currently, only one antiviral drug, remdesivir, has full F.D.A. approval as a Covid treatment. Its use is limited, because patients have to visit a clinic for infusions three days in a row. Paxlovid, a pill, can be taken at home over the course of five days.
Representatives of Pfizer, the manufacturer of Paxlovid, said on Thursday that the company was continuing to study the drug in patients who are immunocompromised or pregnant, as well as for the prevention of long Covid.
Another pill, molnupiravir, also has emergency use authorization as a Covid treatment. But concerns have been raised about its efficacy, prompting regulators in Europe to recommend against its approval there.
In Japan another antiviral pill, called Xocova, has emergency approval. The drug is in a clinical trial in the United States.
The F.D.A. gave emergency use authorization for Paxlovid in December 2021 based on preliminary data from a clinical trial. In that trial, unvaccinated people who were at high risk of severe Covid — people over age 60 or with conditions such as diabetes — saw an 88 percent reduction in their risk of hospitalization.
Pfizer has continued that trial and others. In one study, participants were vaccinated and at high risk, or unvaccinated and at low risk. In the latest analysis, Paxlovid reduced hospitalization and death by 86 percent in unvaccinated, high-risk subjects.
Among high-risk people who were vaccinated, the reduction was 58 percent. People who gained immunity from a previous infection also saw a reduced risk after taking Paxlovid.
The rebound phenomenon gained attention after such famous patients as President Biden and Dr. Anthony Fauci took the drug, tested negative for Covid and then, days later, tested positive again.
The F.D.A. found that a small fraction of people who took Paxlovid experienced a rebound, as did those who took a placebo. In one trial, they estimated that 8.3 percent of people who took Paxlovid tested positive after an initial negative test, compared with 5.7 percent of patients given a placebo.
Yet the rebound seen among those who took Paxlovid was not associated with a longer illness or a worsening of symptoms.
“It’s good to know that this phenomenon exists, but data shows us that in a real-life, clinical sense, it’s not making much of on-the-ground impact in patients,” said Dr. Adi Shah, an infectious disease specialist at the Mayo Clinic who was not on the review panel.
Since December 2021, when Paxlovid received emergency use authorization, federal officials have delivered more than 12.5 million doses nationwide. At the advisers meeting, Pfizer officials said 10 million doses had been taken in the United States and 14 million worldwide.
Yet uptake has been more sluggish than expected. One concern is related to interactions between drugs commonly taken by older adults. The F.D.A. analysis examined that problem, too.
Agency researchers found that a “sizable” proportion of patients who are eligible for Paxlovid also take drugs — whether to lower bad cholesterol or to treat high blood pressure — that can lead to interactions. All told, the F.D.A. has received 147 reports of hospitalizations and six deaths following drug-drug interactions with Paxlovid.
“The drug-drug interactions is a significant concern” that requires ongoing attention, said Dr. Lindsey Baden of Harvard Medical School and chair of the expert committee.
Copyright 2023 The New York Times Company. Reprinted with permission.