The 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 of age and older (weighing ≥45 kg [99.2lbs]). The GSK antibiotic's FDA application is based from the EAGLE-1 phase 3 trial published in The Lancet, showing that gepotidacin (oral, two doses of 3,000mg) was noninferior, with 92.6% (187/202, [95% CI 88·0 to 95·8]) success rates at urogenital site when compared to 91.2% (186/204, [95% CI 86.4-94.7]) success rates for intramuscular ceftriaxone (500mg) plus oral azithromycin (1,000mg) 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 bodyweight over 45 kg, and had suspected uncomplicated urogenital gonorrhea (including mucopurulent discharge), a positive laboratory test 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
What You Need to Know
Gepotidacin, an oral antibiotic from GSK, has been accepted for FDA priority review for treating uncomplicated urogenital gonorrhea in patients aged ≥12 years and weighing ≥45 kg (99.2lbs), with a decision expected by December 11, 2025.
In the EAGLE-1 trial, gepotidacin achieved a 92.6% cure rate, comparable to the 91.2% rate for intramuscular ceftriaxone plus oral azithromycin, with no cases of bacterial persistence and no serious drug-related adverse events.
If approved, gepotidacin would offer a novel, oral treatment for gonorrhea, with a safety profile consistent with prior studies and mostly mild-to-moderate gastrointestinal side effects.
The primary efficacy endpoint 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 (micro-ITT) population, 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 non-inferiority 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 (uUTI).3 A review of regulatory submissions for the uUTI indication is also ongoing in the UK 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. GSK press release. 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 J, et al. Oral gepotidacin for the treatment of uncomplicated urogenital gonorrhea (EAGLE-1): a phase 3 randomised, open-label, non-inferiority, multicentre study. The Lancet. April 14, 2025. Accessed April 15, 2025.
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
