FDA Grants Priority Review for Gepotidacin for Gonorrhea

The US Food and Drug Administration (FDA) has accepted for priority review a supplemental new drug application for gepotidacin as an oral option for the treatment of uncomplicated urogenital gonorrhea in patients 12 years or older (weighing ≥ 45 kg [99.2 lb]). The GSK antibiotic's FDA application is based on the EAGLE-1 phase 3 trial results published in The Lancet, showing that gepotidacin (oral, 2 doses of 3000 mg) was noninferior, with a 92.6% (187 of 202; 95% CI, 88.0%-95.8%) success rate at urogenital site when compared with a 91.2% (186 of 204; 95% CI, 86.4%-94.7%) success rate for intramuscular ceftriaxone (500 mg) plus oral azithromycin (1000 mg) combined therapy.¹

Additionally, there were no failures at the urogenital site due to bacterial persistence of N gonorrhoeae in either treatment arm. The safety and tolerability profile of gepotidacin in the EAGLE-1 trial was consistent with results seen in previous clinical trials, with no serious drug-related adverse events observed in either the gepotidacin or the comparator arm. The most common reported adverse reactions were mild to moderate gastrointestinal events.

A Prescription Drug User Fee Act date for an FDA decision is set for December 11, 2025.

Study Parameters

The EAGLE-1 study was an open-label noninferiority trial examining oral gepotidacin compared with ceftriaxone plus azithromycin. Participants had to have a body weight over 45 kg, and had suspected uncomplicated urogenital gonorrhea (including mucopurulent discharge), a positive laboratory test result for Neisseria gonorrhoeae, or both. Patients were randomly allocated in a 1:1 ratio to each treatment group, stratified by sex and sexual orientation.²

The primary efficacy end point was defined as eradication of gonorrhea at test of cure (days 4-8). The noninferiority margin was prespecified at –10%. The primary outcome was assessed in the microbiological intention-to-treat population, with all participants randomly allocated to a study treatment who received at least 1 dose of their treatment and had confirmed ceftriaxone-susceptible N gonorrhoeae isolated from the baseline culture of their urogenital specimen, the authors explained.²

“Gepotidacin demonstrated noninferiority to ceftriaxone plus azithromycin for urogenital N gonorrhoeae, with no new safety concerns, offering a novel oral treatment option for uncomplicated urogenital gonorrhea,” the authors wrote.²

Other Approvals

This is the second major indication filed in the US for gepotidacin. The antibiotic was FDA approved back in March for uncomplicated urinary tract infections (uUTIs).³ A review of regulatory submissions for the uUTI indication is also ongoing in the United Kingdom and Australia.¹

Learn more: Deciphering When to Use New Novel Agents in Clinical Practice

References
1. Gepotidacin accepted for priority review by the US FDA for the oral treatment of uncomplicated urogenital gonorrhea. Press release. GSK. August 11, 2025. Accessed August 11, 2025.
https://www.gsk.com/en-gb/media/press-releases/gepotidacin-accepted-for-priority-review-by-the-us-fda-for-the-oral-treatment-of-uncomplicated-urogenital-gonorrhoea/
2. Ross JDC, Wilson J, Workowski KA, et al. Oral gepotidacin for the treatment of uncomplicated urogenital gonorrhea (EAGLE-1): a phase 3 randomised, open-label, non-inferiority, multicentre study. Lancet. 2025;405(10489):1608-1620. doi:10.1016/S0140-6736(25)00628-2
3. Parkinson J. Newly FDA-approved UTI antibiotic shows high efficacy for gonorrhea treatment. Contagion. April 15, 2025. Accessed August 12, 2025.
https://www.contagionlive.com/view/newly-fda-approved-uti-antibiotic-shows-high-efficacy-for-gonorrhea-treatment