Pfizer Inc. (NYSE: PFE) today shared top-line results from the Phase 2/3 EPIC-PEP (Evaluation of Protease Inhibition for COVID-19 in Post-Exposure Prophylaxis) study evaluating PAXLOVID™ (nirmatrelvir [PF-07321332] tablets and ritonavir tablets) for post-exposure prophylactic use. In this trial, compared to placebo, Pfizer observed risk reductions of 32% and 37% in adults who received PAXLOVID for five and ten days, respectively, to prevent infection. These results, however, were not statistically significant and, as such, the primary endpoint of reducing the risk of confirmed and symptomatic COVID-19 infection in adults who had been exposed to the virus through a household contact was not met.
Available safety data for PAXLOVID has been generally consistent in more than 3,500 PAXLOVID-treated participants across the EPIC-HR, EPIC-SR and EPIC-PEP studies, as well as in reported post-market safety experience. In EPIC-PEP, this safety profile remained generally consistent when PAXLOVID was used for either five or ten days. Analyses of all secondary endpoints and sub-groups are ongoing, and results will be included in the publication or presentation of the final study results.
“We designed the clinical development program for PAXLOVID to be comprehensive and ambitious with the aim of being able to help combat COVID-19 in a very broad population of patients,” said Albert Bourla, Chairman and Chief Executive Officer, Pfizer. “While we are disappointed in the outcome of this particular study, these results do not impact the strong efficacy and safety data we’ve observed in our earlier trial for the treatment of COVID-19 patients at high risk of developing severe illness, and we are pleased to see the growing global use of PAXLOVID in that population.”
PAXLOVID is currently approved or authorized for conditional or emergency use in more than 60 countries across the globe to treat high-risk COVID-19 patients.
About the Phase 2/3 EPIC-PEP Study
The top-line analysis evaluated data from 2,957 adults. Enrolled adults had a negative SARS-CoV-2 rapid antigen test result and were asymptomatic household contacts with exposure within 96 hours to an individual who was symptomatic and recently tested positive for SARS-CoV-2. Each patient was randomized (1:1:1) to receive orally twice daily one of the following: (i) PAXLOVID for five days followed by placebo for 5 days, (ii) PAXLOVID for ten days or (iii) placebo for ten days.
Recruitment began in September 2021 and was completed during the peak of the COVID-19 Omicron wave.
Additional details on the study are available on clinicaltrials.gov (NCT05047601). Full study data are expected to be released in the coming months and submitted to a peer-reviewed publication.
U.S. FDA Emergency Use Authorization Statement
PAXLOVID has not been approved, but has been authorized for emergency use by FDA under an EUA, for the treatment of mild-to-moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct SARS CoV-2 viral testing, and who are at high-risk for progression to severe COVID-19, including hospitalization or death.
The emergency use of PAXLOVID is only authorized for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of drugs and biological products during the COVID-19 pandemic under Section 564(b)(1) of the Act, 21 U.S.C. § 360bbb-3(b)(1), unless the declaration is terminated or authorization revoked sooner.
PAXLOVID is an inhibitor of CYP3A and may increase plasma concentrations of drugs that are primarily metabolized by CYP3A. Co-administration of PAXLOVID with drugs highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events is contraindicated. Co-administration with other CYP3A substrates may require a dose adjustment or additional monitoring.
Nirmatrelvir and ritonavir are CYP3A substrates; therefore, drugs that induce CYP3A may decrease nirmatrelvir and ritonavir plasma concentrations and reduce PAXLOVID therapeutic effect.
Pregnancy: There are no available human data on the use of nirmatrelvir during pregnancy to evaluate for a drug‑associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Published observational studies on ritonavir use in pregnant women have not identified an increase in the risk of major birth defects. Published studies with ritonavir are insufficient to identify a drug‑associated risk of miscarriage. There are maternal and fetal risks associated with untreated COVID-19 in pregnancy.
Pediatrics: PAXLOVID is not authorized for use in pediatric patients younger than 12 years of age or weighing less than 40 kg. The safety and effectiveness of PAXLOVID have not been established in pediatric patients. The authorized adult dosing regimen is expected to result in comparable serum exposures of nirmatrelvir and ritonavir in patients 12 years of age and older and weighing at least 40 kg as observed in adults, and adults with similar body weight were included in the trial EPIC-HR.
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