Pfizer’s COVID-19 drug did not work for many vaccinated people, according to a new paper from the company’s scientists.
There was not a statistically significant difference between Paxlovid and placebo recipients in terms of time to alleviation of symptoms, the scientists reported in the new paper.
The trial enrolled adults who tested positive for COVID-19, showed at least one COVID-19 symptom, had previously received a COVID-19 vaccine, and had at least one risk factor, such as being a cigarette smoker, for severe COVID-19. Participants were randomized from Aug. 25, 2021, to July 25, 2022.
Of the 1,296 participants, 654 received at least one 300-milligram dose of Paxlovid and at least one 100-milligram dose of ritonavir, a protease inhibitor. The rest received a placebo.
The results showed that the median time to alleviation of COVID-19 symptoms, through day 28, was 12 days in the treatment group and 13 days in the placebo arm. That difference “was not significant,” the authors wrote.
“Similar results were observed in the high-risk subgroup (i.e., participants who had been vaccinated and had at least one risk factor for severe illness) and in the standard-risk subgroup (i.e., those who had no risk factors for severe illness and had never been vaccinated or had not been vaccinated within the previous 12 months),” they added.
Measuring a secondary endpoint, or any COVID-19-related hospitalization or death, researchers found that 0.8 percent of the group that received Paxlovid suffered hospitalization or death, compared to 1.6 percent of placebo recipients. The difference was not statistically significant. The placebo recipients also had on average longer hospital stays and were more likely to be admitted to intensive care units.
The authors said that the results showed “the usefulness of nirmatrelvir–ritonavir in patients who are not at high risk for severe COVID-19 has not been established.”
Limitations of the paper included enrollment of vaccinated people regardless of the time since their last vaccine dose.
Pfizer had previously announced it was stopping enrollment in the trial because of “a very low rate of hospitalization or death observed in the standard-risk patient population.”
Dr. Vinay Prasad, an epidemiology professor at the University of California, San Francisco, who was not involved with the research, said on social media platform X that the trial showed Paxlovid “doesn’t work in vaccinated people.”
“It was embarrassing to watch the administration and many ID doctors recommend this without any credible data,” he wrote, criticizing the government for spending north of $12 billion for courses of the treatment without much trial data.”
Pfizer and the White House did not respond to requests for comment.
A previous Pfizer trial, which was run to assess Paxlovid’s efficacy and safety among the unvaccinated, found that Paxlovid shortened the time to sustained symptoms alleviation and reduced the severity of COVID-19 symptoms. The trial enrolled people with COVID-19, with symptoms, and who had a risk factor for progression to severe disease or were 60 years of age or older.
Based on the results from that trial, the U.S. Food and Drug Administration in 2023 authorized the drug for both unvaccinated and vaccinated adults with mild to moderate COVID-19 who were deemed at high risk for progression to severe COVID-19.
They said, however, that because the trial included few vaccinated people at higher risk, it still appears reasonable to recommend the drug to older people and people with substantial underlying conditions.
Researchers in the new paper also did not detect a difference among drug recipients when compared to placebo recipients in the rebound of viral load, after some previous papers, and patients reported that Paxlovid recipients would experience a rebound of symptoms some days after treatment.
“The study basically discounts the concept of ‘Paxlovid rebound.’ Similar rates of symptom and viral rebound in both groups,” Dr. Adam Gaffney, a doctor with the Cambridge Health Alliance, said on X. “Perceptions of Paxlovid rebound likely a reflection of expectations, narratives, and waxing/waning course of illness.”
