Paxlovid does not significantly alleviate symptoms of COVID-19 compared with placebo among nonhospitalized adults, a new study published April 3 in The New England Journal of Medicine found.
The results suggest that the drug, a combination of nirmatrelvir and ritonavir, may not be particularly helpful for patients who are not at high risk for severe COVID-19. However, although the rate of hospitalization and death from any cause was low overall, the group that received Paxlovid had a reduced rate compared with people in the placebo group, according to the researchers.
“Clearly, the benefit observed among unvaccinated high-risk persons does not extend to those at lower risk for severe COVID-19,” Rajesh T. Gandhi, MD, and Martin Hirsch, MD, of Massachusetts General Hospital in Boston, wrote in an editorial accompanying the journal article. “This result supports guidelines that recommend nirmatrelvir–ritonavir only for persons who are at high risk for disease progression.”
The time from onset to relief of COVID-19 symptoms — including cough, shortness of breath, body aches, and chills — did not differ significantly between the two study groups, the researchers reported. The median time to sustained alleviation of symptoms was 12 days for the Paxlovid group compared with 13 days in the placebo group (P = .60).
However, the phase 2/3 trial found a 57.6% relative reduction in the risk for hospitalizations or death among people who took Paxlovid and were vaccinated but were at high risk for poor outcomes, according to Jennifer Hammond, PhD, head of antiviral development for Pfizer, which makes the drug, and the corresponding author on the study.
Paxlovid has “an increasing body of evidence supporting the strong clinical value of the treatment in preventing hospitalization and death among eligible patients across age groups, vaccination status, and predominant variants,” Dr. Hammond said.
She and her colleagues analyzed data from 1250 adults with symptomatic COVID-19. Participants were fully vaccinated and had a high risk for progression to severe disease or were never vaccinated or had not been in the previous year and had no risk factors for progression to severe disease.
More than half of participants were women, 78.5% were White and 41.4% identified as Hispanic or Latinx. Almost three quarters underwent randomization within 3 days of the start of symptoms, and a little over half had previously received a COVID-19 vaccination. Almost half had one risk factor for severe illness, the most common of these being hypertension (12.3%).
In a subgroup analysis of high-risk participants, hospitalization or death occurred in 0.9% of patients in the Paxlovid group and 2.2% in the placebo group (95% CI, -3.3 to 0.7).
The study’s limitations include that the statistical analysis of COVID-19–related hospitalizations or death from any cause was only descriptive, “because the results for the primary efficacy end point were not significant,” the authors wrote.
Participants who were vaccinated and at high risk were also enrolled regardless of when they had last had a vaccine dose. Furthermore, Paxlovid has a telltale taste, which may have affected the blinding. Finally, the trial was started when the B.1.617.2 (Delta) variant was predominant.
Dr. Gandhi and Dr. Hirsch pointed out that only 5% of participants in the trial were older than 65 years and that other than risk factors such as obesity and smoking, just 2% of people had heart or lung disease.
“As with many medical interventions, there is likely to be a gradient of benefit for nirmatrelvir–ritonavir, with the patients at highest risk for progression most likely to derive the greatest benefit,” Dr. Gandhi and Dr. Hirsch wrote in the editorial. “Thus, it appears reasonable to recommend nirmatrelvir–ritonavir primarily for the treatment of COVID-19 in older patients (particularly those ≥ 65 years of age), those who are immunocompromised, and those who have conditions that substantially increase the risk of severe COVID-19, regardless of previous vaccination or infection status.”
The study was supported by Pfizer.
A version of this article appeared on Medscape.com .