FDA Grants Priority Review to GSK NDA for First-In-Class Oral Antibiotic

The US FDA today accepted GSK’s New Drug Application (NDA) for gepotidacin for the treatment of uncomplicated urinary tract infections (uUTIs) in women who weight at least 40 kg or more and adolescents aged 12 years or older who also weight at least 40 kg.¹

The FDA has granted priority review for this NDA and assigned a Prescription Drug User Fee Act (PDUFA) action date of March 26, 2025, according to a GSK press statement released October 16, 2024. If approved, gepotidacin would be the first in this class of triazaacenaphthylene antibiotics to receive approval for uUTI in over 2 decades, according to GSK.¹

Gepotidacin is an investigational, first-in-class oral triazaacenaphthylene antibiotic with a novel mechanism of action, inhibiting DNA replication via 2 different type 2 topoisomerase enzymes, which should make it harder for pathogens to develop resistance.¹

The NDA was supported by positive results from the pivotal phase 3 trials of gepotidacin in adults and adolescents—EAGLE-2 and EAGLE-3—which were stopped early by their data monitoring committees after interim findings showed clear efficacy.^1,2

The EAGLE-2 and EAGLE-3 studies compared the efficacy and safety of gepotidacin 1500 mg to nitrofurantoin 100 mg, both administered twice a day for 5 days, among 1531 and 1605 female adults and adolescents with uUTI. Results showed that gepotidacin was as effective as nitrofurantoin, the current standard of care for uUTI, at achieving combined clinical and microbiological responses to the infection at 28 days.¹

Specifically, data from EAGLE-3 showed that gepotidacin achieved statistically significant superiority compared to nitrofurantoin, demonstrating therapeutic success in 58.5% of individuals vs 43.6% for nitrofurantoin (treatment difference 14.6%, 95% CI 6.4-22.8). In EAGLE-2, gepotidacin had therapeutic success in 50.6% of participants compared to 47.0% for nitrofurantoin (treatment difference 4.3%, 95% CI -3.6 to 12.1), according to GSK.¹

In both trials, the safety and tolerability profile of gepotidacin was consistent with previous studies of the drug. The most common adverse events reported by participants who received gepotidacin were gastrointestinal-related, including diarrhea and nausea, and were mostly mild or moderate in severity. The phase III clinical program for gepotidacin also includes the noninferiority urogenital gonorrhea trial, EAGLE-1. This study compared efficacy and safety of gepotidacin to ceftriaxone plus azithromycin in 628 participants who had uncomplicated urogenital gonorrhea caused by Neisseria gonorrhoeae.¹

References:

1. Gepotidacin accepted for priority review by US FDA for treatment of uncomplicated urinary tract infections in female adults and adolescents. News release. GSK. October 16, 2024. Accessed October 16, 2024. https://www.gsk.com/en-gb/media/press-releases/gepotidacin-accepted-for-priority-review-by-us-fda-for-treatment-of-uncomplicated-urinary-tract-infections-in-female-adults-and-adolescents/
2. EAGLE-2 and EAGLE-3 phase III trials for gepotidacin stopped early for efficacy following pre-planned interim analysis by Independent Data Monitoring Committee. News release. GSK. November 3, 2022. Accessed October 16, 2024. https://www.gsk.com/en-gb/media/press-releases/gsk-announces-phase-iii-trials-for-gepotidacin/