Drug News

Paxlovid’s Effectiveness Fades in Face of New Variants

A real-world study recently published in JAMA Open Network sheds light on the evolving effectiveness of Pfizer’s COVID-19 antiviral medication, Paxlovid, and its comparison to Merck’s antiviral, Lagevrio, in high-risk patients. The study indicates that Paxlovid’s ability to prevent hospitalization or death in high-risk patients has declined compared to earlier clinical trials, although it remains highly effective in preventing death alone.

In this study, which drew data from electronic health records of 68,867 patients diagnosed with COVID-19 in hospitals in Cleveland and Florida between April 1, 2022, and February 20, 2023, Paxlovid exhibited an approximately 37% effectiveness at preventing death or hospitalization in high-risk patients when compared to those receiving no treatment. Lagevrio, developed by Merck, demonstrated slightly higher efficacy at around 41%.

However, when considering death as the sole endpoint, Paxlovid remained notably effective at around 84%, surpassing Lagevrio’s 77% efficacy. These real-world effectiveness rates appear lower than the impressive 86% effectiveness rate for Paxlovid observed in the initial clinical trials conducted in 2021.

Several factors may account for the variance in effectiveness between real-world and clinical studies. The initial trials predominantly included unvaccinated individuals, while real-world scenarios encompass vaccinated and potentially different populations. Additionally, the SARS-CoV-2 virus has continued to evolve since the early clinical trials, with the emergence of new variants, such as the Omicron subvariants, which might influence the drugs’ performance.

Despite the decreased effectiveness, the study still endorses the use of both Paxlovid and Lagevrio, as they effectively reduce hospitalization and death among high-risk COVID-19 patients, even when considering recent Omicron subvariants. The study findings emphasize that both nirmatrelvir (Paxlovid) and molnupiravir (Lagevrio) can be used for the treatment of non-hospitalized high-risk patients infected with Omicron, regardless of factors like age, race, ethnicity, virus strain, vaccination status, previous infection status, or coexisting conditions.

It is important to note that these antiviral drugs should be administered within five days of the onset of COVID-19 symptoms to maximize their effectiveness in reducing the severity of the disease and preventing hospitalization or death. This real-world study contributes valuable insights into the evolving landscape of COVID-19 therapeutics and their effectiveness in high-risk patient populations.


JAMA Network Open: “Nirmatrelvir or Molnupiravir Use and Severe Outcomes From Omicron Infections.”

FDA: “FDA Approves First Oral Antiviral for Treatment of COVID-19 in Adults.”

Bloomberg: “Paxlovid Is Now Less Effective Against Covid, Study Shows.”

READ: 10 Paxlovid Side Effects You Should Not Ignore


Dr. Oche Otorkpa PG Cert, MPH, PhD

Dr. Oche is a seasoned Public Health specialist who holds a post graduate certificate in Pharmacology and Therapeutics, an MPH, and a PhD both from Texila American University. He is a member of the International Society of Substance Use Professionals and a Fellow of the Royal Society for Public Health in the UK. He authored two books: "The Unseen Terrorist," published by AuthorHouse UK, and "The Night Before I Killed Addiction."
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