(P113) EFFICACY AND SAFETY OF ORAL GEPOTIDACIN FOR UNCOMPLICATED UROGENITAL GONORRHEA: HIV AND OTHER SUBGROUP ANALYSES FROM A RANDOMIZED PHASE 3 TRIAL (EAGLE-1)

Background:
A Phase 3 trial (EAGLE-1) demonstrated that oral gepotidacin, a first-in-class triazaacenaphthylene bactericidal antibiotic, was efficacious in treating uncomplicated urogenital gonorrhea (uUGC) and had a safety profile consistent with Phase 1/2 data. Prespecified efficacy and safety subgroup analyses are presented.

Methods:
EAGLE-1 (NCT04010539) was a Phase 3, randomized, open-label, sponsor-blinded, non‑inferiority trial comparing two doses of oral gepotidacin (3000mg) with intramuscular ceftriaxone (500mg) plus oral azithromycin (1g) for the treatment of uUGC. Microbiological success was defined as culture-confirmed eradication of Neisseria gonorrhoeae from the urogenital body site at test-of-cure (Day 4–8). Unable-to-determine microbiological data (e.g. missing data, non-study antibiotic use) at test-of-cure were considered microbiological failure. Microbiological success was evaluated by participant HIV-status, geographic region, sex/sexual orientation combination, multiple body sites of infection (yes/no), and Chlamydia trachomatis and/or Mycoplasma genitalium co-infection, amongst others.

Results:
Of 628 participants enrolled, 559 (89%) were male, 439 (70%) men who have sex with men, 69 (11%) female, and median age was 32 years. 406 met criteria for the microbiological intent-to-treat population and were included in efficacy analyses. Across subgroups, microbiological success rates were generally similar between the gepotidacin and ceftriaxone/azithromycin arms. Among participants with (n=78) and without (n=318) HIV, microbiological success rates were 38/43 (88.4%) and 147/155 (94.8%) in the gepotidacin arm, respectively. Microbiological success rates were 31/35 (88.6%) and 149/163 (91.4%) in ceftriaxone/azithromycin arm, respectively. There were no cases of urogenital bacterial persistence in any subgroup. All failures were due to unable-to-determine outcomes. AEs were more common in the gepotidacin arm irrespective of subgroup, driven by gastrointestinal events. AEs were mostly mild-to-moderate in nature.

Conclusion:
Overall, gepotidacin consistently demonstrated high levels of microbiological success irrespective of sex/sexual orientation combination, geographic region, bacterial co-infection, and HIV. No new safety concerns were identified. Gepotidacin has potential as a novel oral treatment for uUGC in key patient populations.