The Food and Drug Administration’s (FDA) Antimicrobial Drugs Advisory Committee voted 16 to 1 that the available data support the safety and effectiveness of Paxlovid™ (nirmatrelvir tablets and ritonavir tablets) for the treatment of mild to moderate COVID-19 in adult patients who are at high risk for progression to severe illness.
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.
During the committee meeting, the panel reviewed data from the EPIC clinical development program, which includes 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. 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).
Data from the phase 2/3 EPIC-SR study (ClinicalTrials.gov Identifier: NCT05011513) was also evaluated during the meeting. 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.
Real-world evidence was also presented to the committee and reflected the findings from clinical trials. Paxlovid was found to be effective in both vaccinated individuals and those who developed natural immunity.
With regard to Paxlovid treatment and COVID-19 rebound, an analysis of available data did not show a clear association. As stated in the FDA briefing document, “Overall, these findings indicate that in a subset of SARS-CoV-2 infections, virologic and/or symptomatic rebound may occur as part of the natural progression and resolution of COVID-19 disease, irrespective of Paxlovid treatment.”
While not bound by the committee’s recommendations, the FDA does take them into consideration when making final decisions on approval. Paxlovid is currently authorized for emergency use for the treatment of adults and pediatric patients (12 years of age and older weighing at least 40kg) with a current diagnosis of mild to moderate COVID-19 and who are at high risk for progression to severe COVID-19, including hospitalization or death.
“We are encouraged by the AMDAC’s positive vote today,” said James Rusnak, Senior Vice President and Chief Development Officer, Internal Medicine, Anti-infectives and Hospital, Pfizer. “The outcome is well supported by the strong safety and efficacy data seen both in our clinical trials and in a growing base of real-world evidence, showing that Paxlovid helps to reduce the risk of hospitalization or death for high-risk adult patients regardless of vaccination status.”
The Prescription Drug User Fee Act action date has been set for May 2023.
- FDA advisory committee votes in support of favorable benefit-risk profile for Pfizer’s Paxlovid™. News release. Pfizer. March 16, 2023. https://www.businesswire.com/news/home/20230316005635/en/FDA-Advisory-Committee-Votes-in-Support-of-Favorable-Benefit-Risk-Profile-for-Pfizer%E2%80%99s-PAXLOVID%E2%84%A2.
- FDA briefing document. Nirmatrelvir tablets and ritonavir tablets copackaged for oral use. FDA. Accessed March 16, 2023. https://www.fda.gov/media/166197/download.