Pfizer Study Questions Paxlovid's Efficacy as 'Miracle Drug'—Is It Still Worth Taking?

Last weekend, a study led by the head of Pfizer's antiviral drug development showed that Paxlovid (referred to as "P drug"), known as the "COVID wonder drug" during the pandemic, did not have a significant effect in shortening the duration of persistent COVID symptoms.

This Phase 2/3 clinical trial, conducted by Dr. Jennifer Hammond, head of antiviral drug development at Pfizer, Inc., and her colleagues from July 2021 to July 2022, was published nearly two years later in the New England Journal of Medicine, raising questions about the efficacy of Pfizer's Paxlovid.

The study authors concluded: "The effectiveness of Paxlovid for COVID-19 patients at low risk of severe illness has not been determined."

The First Financial reporter sent an email to Dr. Hammond for comments, and had not received a response as of press time.

The trial randomly assigned 1,296 participants in a 1:1 ratio to receive Paxlovid or a placebo every 12 hours within 5 days of the onset of COVID-19 symptoms, for a duration of 5 days. Among them, 654 participants took Paxlovid, and 634 participants took the placebo.

Participants included patients who were fully vaccinated and had at least one risk factor for severe illness, as well as patients without such risk factors but who had never been vaccinated against COVID-19 or had not been vaccinated in the past year. The most common risk factors were obesity, smoking, and hypertension.

The primary endpoint of this clinical trial was the duration of symptom relief from COVID-19. The results showed that for those who were fully vaccinated against COVID-19 but had at least one significant risk factor, the median time for the P drug group to achieve sustained relief of all targeted signs and symptoms of COVID-19 was 12 days, compared to 13 days in the placebo group. This indicates that the antiviral drug Paxlovid has almost no effect on shortening the duration of symptoms.

The secondary endpoint of the trial was hospitalization due to COVID-19 or all-cause mortality. In the P drug group, five participants were hospitalized or died due to COVID-19, while in the placebo group, ten participants were hospitalized or died due to COVID-19. The authors wrote: "Although the difference in the number of hospitalizations and all-cause deaths related to COVID-19 in this trial was not significant, it is consistent with recent real-world data."

It is worth noting that the trial mainly included younger participants, with an average age of 42, and only 5% of the participants were over 65 years old. Therefore, the results of this study may not be applicable to elderly patients.

In a commentary published alongside the study, Professor Rajesh Gandhi and Professor Martin Hirsch of Massachusetts General Hospital and Harvard Medical School in the United States noted, "As with many medical interventions, Paxlovid may offer a gradient of benefit, with those at higher risk of disease progression being more likely to benefit." The commentary also stated that long-term studies of Paxlovid are necessary to understand the extent to which the drug provides protection against long-term COVID-19.

Dr. Michael Osterholm, director of the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota, commented in an article published by the university: "The younger participant demographic has changed how this study defines risk. The risk factors for an unvaccinated 18-year-old are clearly different from those of a vaccinated 89-year-old. We should avoid overgeneralizing the study results to older adults and high-risk populations. For these individuals, Paxlovid remains a useful first-line treatment option."

Due to the sharp decline in demand for COVID-19 therapies, it has also impacted the performance of Pfizer, a manufacturer of COVID-19 drugs. Over the past year, Pfizer's stock price has fallen by more than 35%.

However, the research and development of COVID-19 drugs are still ongoing. In January this year, Chinese researchers published a research article in The New England Journal of Medicine, stating that a Phase 2/3 clinical trial of oral Simnotrelvir for treating mild to moderate COVID-19 adult patients showed that early administration of Simnotrelvir combined with Ritonavir could shorten the time to symptom resolution in adult patients with COVID-19, with no significant safety issues observed.

Professor Lu Hongzhou from the Third People's Hospital of Shenzhen, as the co-first author of this paper, told the First Financial Reporter that he believed the effect of a "single drug" might be better because there would be no interaction between drugs.

Zhang Wenhong, director of the Department of Infectious Diseases at Huashan Hospital, Fudan University, and head of the National Medical Center for Infectious Diseases (Shanghai), also pointed out that an important issue faced during the clinical trial phase is the lack of a standard for evaluating clinical efficacy — specifically, what primary endpoint should be used as the criterion for assessing efficacy, especially given the rapid evolution of COVID-19 and the swift decline in the rate of severe cases among high-risk populations.

Editorial Responsibility: Liu Wanli SF014