580. Pharmacokinetics (PK) and Safety of Nirmatrelvir/Ritonavir (NMV/r) in Non-Hospitalized Symptomatic Pediatric Patients Ages 6 Years and Older with COVID-19 who are at Increased Risk of Progression to Severe Disease (EPIC-Peds)
Authors: Gerhart Jacqueline , Leister-Tebbe Heidi , Singh Namita , Chan Phylinda L S , Shi Haihong , Carey William D H , Yan Jean , Lynn Baniecki Mary , Hendrick Victoria , Wisemandle Wayne , Singh Ravi Shankar P , Hammond Jennifer 
Published: January 2025

Abstract

Background
NMV/r is an antiviral treatment for mild-to-moderate COVID-19 approved for high-risk adults and authorized for high-risk adolescents ≥ 12 years weighing ≥ 40 kg under Emergency Use Authorization. EPIC-Peds evaluates PK, safety, and efficacy in pediatrics. Here we report data in patients ≥ 6 years.

Methods
EPIC-Peds is an interventional Phase 2/3 open-label study. NMV/r was administered orally twice daily (BID) for 5 days to 75 participants ≥ 6 years weighing ≥ 40 kg (Cohort 1) and weighing ≥ 20 kg to &lt; 40 kg (Cohort 2) with symptomatic COVID-19 who were at risk of progression to severe disease. Efficacy was extrapolated from adults by matching pediatric exposure to adult COVID-19 patients receiving the indicated NMV/r dose. Sparse PK samples were collected on treatment Day 1 and 5 and incorporated into a previously developed Population PK model, which was used to simulate pediatric exposure. Safety was evaluated through Day 34. Supportive efficacy endpoints included COVID-19 related hospitalization, all-cause death, and change in SARS-CoV-2 nasopharyngeal (NP) RNA concentration from baseline to end of treatment.

Results
NMV/r was safe and well-tolerated in pediatric participants. Overall, 26.7% of participants reported an all-causality adverse event (AE), with diarrhea and headache the most frequently reported in 3 (4%) participants each. AEs were mostly mild or moderate in severity, nonserious, and unrelated to treatment. Seven treatment-related AEs were reported, and none led to treatment discontinuation. No treatment-related serious AEs were reported. Simulated pediatric exposure of NMV/r of 300 mg/100 mg BID for Cohort 1 and 150 mg/100 mg BID for Cohort 2 showed &gt; 90% of subjects achieving trough concentration (Cmin) above the 90% effective concentration (EC90) after the first dose and at steady state (Table 1). There were no COVID-19 related hospitalizations or all-cause deaths. The adjusted mean decrease in SARS-CoV-2 NP RNA concentration from baseline to end of treatment was ≥ -3.4 log10 copies/mL, numerically greater than in adults.

Conclusion
In pediatric patients ages 6 years and older, 300 mg/100 mg BID and 150 mg/100 mg BID NMV/r dosing for patients weighing ≥ 40 kg and ≥ 20 to &lt; 40 kg, respectively, was safe and effective, with NMV Cmin &gt; EC90 in &gt; 90% of the population for both groups.

Disclosures
Jacqueline Gerhart, PhD, MBA, MS, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Heidi Leister-Tebbe, BSN, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds (Public Company) Namita Singh, MD, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Phylinda L. S. Chan, PhD, Pfizer: Stocks/Bonds (Public Company) Haihong Shi, MS, MBA, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) William D H Carey, N/A, MBBS, PhD, MRCPI, Pfizer: Employee with stock options|Pfizer: Stocks/Bonds (Public Company) Jean Yan, M.S., Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Mary Lynn Baniecki, PhD, Pfizer: salaried employee|Pfizer: Stocks/Bonds (Public Company) Victoria Hendrick, BSc, Pfizer: Stocks/Bonds (Private Company)|Pfizer: Stocks/Bonds (Public Company) Wayne Wisemandle, MA, Pfizer: Employee of Pfizer|Pfizer: Stocks/Bonds (Public Company) Ravi Shankar P. Singh, PhD, FCP, EMD Serono: Employer of Spouse|Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds (Public Company) Jennifer Hammond, PhD, Pfizer, Inc: Employee|Pfizer, Inc: Stocks/Bonds (Public Company)