The New Drug Application (NDA) for Paxlovid has been submitted to the Food and Drug Administration (FDA). Pfizer is seeking approval of the oral antiviral therapy for both vaccinated and unvaccinated patients who are at high risk for progression to severe illness from 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 NDA includes data from the phase 2/3 EPIC-HR study (ClinicalTrials.gov Identifier: NCT04960202), which compared the efficacy and safety of Paxlovid to placebo in patients with a laboratory-confirmed SARS-CoV-2 infection within a 5-day period with mild to moderate symptoms. Results from the final Clinical Study Report showed Paxlovid reduced the risk of hospitalization or death from any cause by 86% in patients treated within 5 days of symptom onset compared with placebo (P <.0001).

The submission also includes data from the EPIC-SR study (ClinicalTrials.gov Identifier: NCT05011513), which enrolled standard risk individuals who had a confirmed diagnosis of SARS-CoV-2 infection within 5 days prior to randomization; onset of symptoms within 5 days of randomization; and at least 1 characteristic or underlying medical condition associated with an increased risk of developing severe illness and were fully vaccinated against COVID-19 or, no characteristics associated with an increased risk of severe COVID-19 and were unvaccinated. Among 1153 patients enrolled through December 2021, treatment with Paxlovid showed a nonsignificant 51% relative risk reduction in hospitalization or death. Among 721 vaccinated adults with at least 1 risk factor, treatment with Paxlovid showed a nonsignificant 57% relative risk reduction.

An integrated analysis of data across both studies showed an 84% reduction (P <.0001) in hospitalizations or death, compared with placebo and regardless of vaccination status, in patients with at least 1 risk factor for progression to severe COVID-19 illness who were treated with Paxlovid within 5 days of symptom onset. Viral load reduction was also observed to be consistent across all studies.

The application also includes safety data from more than 3500 patients treated with Paxlovid in clinical trials as well as postauthorization experiences. With regard to “COVID-19 rebound”, the data showed that the frequency of return of detectable nasal viral RNA following treatment was low and generally similar between the treatment and placebo groups.

“Data from our clinical development program, coupled with the more than 1.7 million patients around the world who have been prescribed our oral treatment to date, reinforce Paxlovid as an important treatment option for mild to moderate COVID-19 in patients at greater risk of progression to severe symptoms, regardless of vaccination status,” said Albert Bourla, Chairman and Chief Executive Officer, Pfizer. “We look forward to working with the FDA toward full regulatory approval for Paxlovid.”

Reference

Pfizer announces submission of New Drug Application to the US FDA for Paxlovid. News release. June 30, 2022. https://www.businesswire.com/news/home/20220630005126/en/Pfizer-Announces-Submission-of-New-Drug-Application-to-the-U.S.-FDA-for-PAXLOVID%E2%84%A2