Doubts about Pfizer's flagship antiviral: No reduction in hospitalizations or deaths in adults

A new study published in the New England Journal of Medicine (NEJM) has reignited the debate over the efficacy of the antiviral drug Paxlovid, developed by Pfizer, especially in vaccinated adults considered at high risk for covid.

Study results: No significant reduction in hospitalizations or deaths

The analysis is based on two large open-label clinical trials, PANORAMIC (United Kingdom) and CanTreatCOVID (Canada), which included about 3,500 participants. Both concluded that treatment with nirmatrelvir and ritonavir (Paxlovid) did not reduce the incidence of hospitalization or death in vaccinated high-risk patients who had recently contracted covid.

The authors pointed out that specific subgroups were also not identified as clearly benefiting from the treatment, which calls into question its usefulness in the current context of high population immunity.

Strong public investment and initial expectations

The Biden Administration directed more than $12 billion to purchase Paxlovid, acquiring nearly 24 million treatments. This bet was based on previous results, especially Pfizer's EPIC-HR trial, which showed benefits in early stages of the pandemic, when the population was not widely vaccinated.

However, the new data suggest that those results are not extrapolable to the current context, characterized by mass vaccination and different variants of the virus.

NEJM editorial: Caution on the conclusions

On the same day the study was published, the NEJM included an editorial signed by Anthony Fauci and Cliff Lane, who called for caution in interpreting the results.

Although they acknowledged that benefits in reduced hospitalization are not evident, they argued that Paxlovid could still be useful in certain cases, such as in immunocompromised individuals or older adults. They also noted that the antiviral could speed recovery and reduce viral load.

The study was completed approximately 19 months before publication, which has generated criticism among some experts. Renowned cardiologist Venk Murthy, of the University of Michigan, called the delay "surprising," while other analysts suggest possible conflicts of interest or pressures related to the commercial impact of the drug.

The design of the trials has also been questioned, being open-label and placebo-free, which could influence subjective variables such as the perception of symptom improvement.

Scientific interpretation: Evolving pandemic context

Experts such as cardiologist John Mandrola have stressed that the results reflect a common phenomenon in medicine: the loss of efficacy of interventions as epidemiological conditions change.

In this case, the combination of widespread vaccination, prior immunity, and virus evolution would have reduced the margin of clinical benefit of Paxlovid in the general at-risk population.

The new study raises serious doubts about the current role of Paxlovid in preventing serious complications of COVID-19 in high-risk vaccinated adults. Although it may retain utility in specific cases, the data suggest that its impact is more limited than initially thought.

The debate now centers on how to adjust clinical recommendations and public policy in light of this evidence, in a context where the pandemic has changed significantly since its early phases.