The Food and Drug Administration (FDA) has approved Paxlovid (nirmatrelvir tablets and ritonavir tablets, co-packaged for oral use) for the treatment of mild to moderate COVID-19 in adults who are at high risk for progression to severe COVID-19, including hospitalization or death. This is the first approval of an oral antiviral therapy for COVID-19.
Paxlovid consists of nirmatrelvir and low-dose ritonavir. Nirmatrelvir inhibits the viral replication of SARS-CoV-2 by blocking the activity of the SARS-CoV-2 3CL protease. Coadministration with low-dose ritonavir slows the metabolism of nirmatrelvir and prolongs its activity.
The approval was based on data from the EPIC clinical development program, which included the phase 2/3 EPIC-HR study (ClinicalTrials.gov Identifier: NCT04960202). This study enrolled unvaccinated adults with laboratory-confirmed SARS-CoV-2 infection and mild to moderate symptoms.
Patients were required to have at least 1 characteristic or underlying medical condition associated with an increased risk of developing severe illness from COVID-19. In this study, 977 patients received Paxlovid and 989 received placebo. Results showed that Paxlovid reduced the risk of hospitalization or death from any cause through day 28 by 86% (95% CI, 72-93) in patients treated within 5 days of symptom onset compared with placebo (P <.0001).
During the 28 days of follow-up, 0.9% of Paxlovid-treated patients and 6.5% of placebo patients were hospitalized due to COVID-19 or died from any cause. Among those with prior immunity, the risk of COVID-19-related hospitalization or death from any cause during 28 days of follow-up was 0.2% and 1.7% in the Paxlovid (n=490) and placebo (n=479) groups, respectively.
Data from the phase 2/3 EPIC-SR study (ClinicalTrials.gov Identifier: NCT05011513) was also included in the agency’s review. While this trial failed to demonstrate a meaningful difference for the primary endpoint of time to sustained alleviation of all symptoms for 4 consecutive days, a numerically lower rate of COVID-19 hospitalization or death was observed in a subgroup of nonhospitalized, vaccinated high-risk individuals.
Findings from EPIC-HR and EPIC-SR also showed that rebound in SARS-CoV-2 (RNA or virus) shedding or COVID-19 symptoms occurred in a subset of patients, both in the Paxlovid and placebo arms. An analysis of currently available data did not show a clear association between Paxlovid and COVID-19 rebound.
“Today’s approval demonstrates that Paxlovid has met the agency’s rigorous standards for safety and effectiveness, and that it remains an important treatment option for people at high risk for progression to severe COVID-19, including those with prior immunity,” said Patrizia Cavazzoni, MD, director for the FDA’s Center for Drug Evaluation and Research. “The FDA remains committed to working with sponsors to facilitate the development of new prevention and treatment options for COVID-19.”
To ensure continued access, Paxlovid manufactured and packaged under the Emergency Use Authorization (EUA) and distributed by the US Department of Health and Human Services will continue to be available to those not covered by the FDA’s approval (eg, eligible children 12 to less than 18 years of age).
The FDA-approved prescribing information can be found here.
- FDA approves first oral antiviral for treatment of COVID-19 in adults. News release. May 25, 2023. https://www.prnewswire.com/news-releases/fda-approves-first-oral-antiviral-for-treatment-of-covid-19-in-adults-301834804.html.
- Paxlovid. Package insert. Pfizer; 2023. Accessed May 25, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217188s000lbl.pdf.