2831. Efficacy and Safety of Gepotidacin for Uncomplicated Urinary Tract Infection: Pooled Subgroup Analyses of the EAGLE-2 and EAGLE-3 Randomized Phase 3 Trials

BACKGROUND: Two large Phase 3 trials showed that gepotidacin, a first-in-class oral triazaacenaphthylene bactericidal antibiotic, was efficacious in treating uncomplicated urinary tract infection (uUTI) in females and had an acceptable safety profile consistent with prior gepotidacin trials. We now present a pooled analysis of the EAGLE-2 and EAGLE-3 trials to evaluate gepotidacin efficacy and safety in patient subgroups. METHODS: Data were pooled from EAGLE-2 and EAGLE-3, near identical global, Phase 3, randomized, double-blind, double-dummy, active-controlled non-inferiority trials comparing oral gepotidacin (1500mg) to nitrofurantoin (100mg), both twice daily for 5 days. Females aged ≥ 12 years with ≥ 2 uUTI symptoms were eligible. Therapeutic success (combined clinical and microbiological success) was determined at the test-of-cure visit (Day 10–13) for patient subgroups – age, geographic region, history of recurrent uUTI, diabetes, and renal function. Efficacy subgroup analyses were conducted in the pooled microbiological intent-to-treat population of patients with baseline uropathogens (≥ 10(5) CFU/mL) susceptible to nitrofurantoin (micro-ITT NTF-S) and were adjusted for study. Pooled adverse event (AE) data for the overall population are presented. RESULTS: Both studies stopped early for efficacy (per independent data monitoring committee review). Among 1201 patients in the pooled micro-ITT NTF-S population, mean age was 51.5 years; 54% were aged > 50 years (Table 1). Across subgroups, differences in therapeutic success numerically favored gepotidacin vs nitrofurantoin (Table 2). Treatment differences were higher for > 50 years vs other age groups and for mild renal impairment vs normal renal function, and were similar within other subgroups. AEs were reported in 35% (gepotidacin) and 23% (nitrofurantoin) of patients (Table 3); most were mild to moderate and gastrointestinal in nature. There were few serious AEs. [Figure: see text] [Figure: see text] [Figure: see text] CONCLUSION: Gepotidacin generally demonstrated consistent therapeutic efficacy in patient subgroups, including patients aged > 50 years and those with a history of recurrent uUTI (subgroups at higher risk of treatment failure). There were no new or concerning safety signals. Gepotidacin has potential as a novel oral treatment for uUTI in key patient subgroups. DISCLOSURES: Thomas M. Hooton, MD, GSK: Advisor/Consultant Caroline R. Perry, PhD, GSK: Employee and shareholder Salim Janmohamed, MD, GSK: Employee and shareholder Amanda Sheets, PhD, GSK: Employee and shareholder Jeremy Dennison, MD, GSK: Employee and shareholder Helen Millns, PhD, GSK: Employee and shareholder Emily Jarvis, MSc, GSK: Employee and shareholder Chun Huang, PhD, GSK: Employee and shareholder