BAMLANIVIMAB PLUS ETESEVIMAB for the TREATMENT of COVID-19 in PEDIATRIC PATIENTS

ABSTRACT

Background: There are no authorized or approved treatments in the US for COVID-19 in patients <12 years of age. SARS-CoV-2 neutralizing monoclonal antibodies bamlanivimab and etesevimab together (BAM+ETE) reduce COVID-19 related hospitalization and all-cause mortality in patients ≥12 years of age with mild to moderate COVID-19. Herein, we present the pharmacokinetic (PK), safety, and efficacy results from an open-label Phase III clinical trial addendum (BLAZE-1, NCT04427501) investigating weight-based dosing of BAM+ETE in pediatric patients at increased risk for severe COVID-19. Methods: A total of 91 pediatric patients (<18 years of age) were evaluated for PK. Pediatric patients weighing ≥40kg received 700mg BAM+1400mg ETE. Pediatric patients weighing less than 40kg received weight-based dosing to match the exposures observed in adults and adolescents (12 to <18 years of age) who received the authorized dose of 700mg BAM+1400mg ETE. Twenty additional adolescent patients (12 to <18 years of age) received BAM+ETE in controlled BLAZE-1 cohorts and were included in safety and efficacy analyses. All ambulatory patients had mild to moderate COVID-19 upon enrollment, at least one risk factor for severe COVID-19, and received treatment within 3 days of a positive SARS-CoV-2 test. The primary objective was to characterize the pharmacokinetics of weight-based dosing of BAM+ETE in pediatric patients. Results: Of the 111 pediatric patients who received BAM+ETE, the median age was 12 and age distribution was 12 to <18 (n=60), 6 to <12 (n=36), 2 to <6 (n=10), and 0 to <2 (n=5). Overall, 47.7% were female, 19.1% were Hispanic/Latino, and 62.4% were Black/African American. In patients receiving weight-based dosing, the AUC for both BAM and ETE in pediatric patients was similar (within 90% interval) to adults (Figure). For all pediatric patients, there were no reports of hospitalizations, serious adverse events, or deaths. At Day 7, pediatric patients had a change in viral load from baseline of-4.10 (normalized baseline viral load of 6.41) as compared to-3.65 (normalized baseline viral load of 6.75) in adult patients. The median time to complete symptom resolution was 5 days for all pediatric patients. Conclusion: The weight-based doses administered to pediatric patients provided similar drug exposures when compared to adult patients who received the authorized dose of 700 mg BAM+1400mg ETE. Treatment in pediatric patients was well-tolerated and resulted in favorable viral load reduction and symptom resolution.