| Description: |
Background Two Phase 3 trials (EAGLE-2 [NCT04020341]/EAGLE-3 [NCT04187144]) showed that gepotidacin, a first-in-class triazaacenaphthylene antibacterial, was non-inferior to nitrofurantoin (NTF) in treating uncomplicated urinary tract infection (uUTI) caused by NTF-susceptible (NTF-S) qualifying uropathogens (≥ 105 CFU/mL).1 This study evaluates gepotidacin efficacy in the pooled EAGLE-2/3 microbiological intent-to-treat (micro-ITT) NTF not susceptible (NTF-NS) population. Methods In EAGLE-2/3, female patients aged ≥ 12 years with ≥ 2 uUTI symptoms received oral gepotidacin (1500mg) or NTF (100mg) twice-daily for 5 days.1 In this study, therapeutic, clinical and microbiological response (defined in tables) at test-of-cure (Day 10–13) were assessed in the pooled EAGLE-2/3 micro-ITT NTF-NS and NTF-S populations and across patient subgroups. Results Of the 1421 micro-ITT patients, 220 (15%) had NTF-NS uropathogens and 1201 (85%) had NTF-S uropathogens. The most common baseline uropathogens were Escherichia coli (90%) in the NTF-S population, and Klebsiella pneumoniae (31%), Proteus mirabilis (26%), and E. coli (24%) in the NTF-NS population (Table 1). Across key subgroups, the proportion of patients with NTF-NS uropathogens was broadly similar to the overall population (except Hispanic/Latinx, Black race and US subgroups which were numerically higher; Figure 1). For efficacy outcomes, treatment differences were higher in the NTF-NS vs the NTF-S population, and, as expected, favored gepotidacin vs NTF (Table 2). Treatment differences in therapeutic success were numerically higher across key subgroups in the NTF-NS vs the NTF-S population (Figure 2). Conclusion Gepotidacin was efficacious in both populations, and across subgroups, with a higher therapeutic treatment difference in the NTF-NS vs the NTF-S population. Gepotidacin could offer benefit in patients with uUTI, including those with NTF-NS uropathogens. 1. Wagenlehner F, et al. Lancet 2024;403:741–55. Funding: EAGLE-2 was funded in part by GSK and in ... |