FDA approves gepotidacin for uncomplicated UTI

Today, March 25, 2025, the FDA approved gepotidacin (Blujepa) for the treatment of female adults (40 kg and over) and adolescents (aged 12 years and older; 40 kg and over) with uncomplicated urinary tract infections (UTIs) that are caused by the following susceptible microorganisms: Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii complex, Staphylococcus saprophyticus and Enterococcus faecalis, GSK announced in a news release.¹

In EAGLE-3, gepotidacin demonstrated superiority to nitrofurantoin in the treatment of uUTI.

According to GSK, gepotidacin is the first in a new class of oral antibiotics for uUTIs in nearly 30 years.

“For many, uUTIs can be a burden that severely impacts daily life," said Thomas Hooton, MD, professor of clinical medicine at the University of Miami School of Medicine, in the news release.¹ "With an increasing number of patients experiencing recurrent infections, there remains a clear need for continued research of antimicrobials to help address ongoing patient challenges and the strain on healthcare systems.”

According to GSK, gepotidacin is a “bactericidal, first-in-class triazaacenaphthylene antibiotic that inhibits bacterial DNA replication by a distinct binding site, a novel mechanism of action, and for most pathogens, provides well-balanced inhibition of two different Type II topoisomerase enzymes.”²

The commercial launch of gepotidacin in the US is planned for the second half of 2025, the company reported.

Data on gepotidacin

The approval is backed by data from the phase 3 EAGLE-2 (NCT04020341) and EAGLE-3 (NCT04187144) trials.^2,3

In EAGLE-2, gepotidacin demonstrated non-inferiority to nitrofurantoin, the previous standard of care for uUTI, in female adults (40 kg and over) and adolescents (aged 12 years and older; 40 kg and over). In total, the EAGLE-2 trial enrolled 607 patients who were randomly assigned 1:1 to receive 1500 mg gepotidacin twice daily (n = 320) or 100 mg nitrofurantoin twice daily (n = 287) for 5 days.

Therapeutic success (composite of clinical success plus microbiological success) was achieved in 50.6% of patients in the gepotidacin arm vs 47% of patients in the nitrofurantoin arm (treatment difference, 4.3%; 95% CI, -3.6% to 12.1%).

In EAGLE-3, gepotidacin demonstrated statistically significant superiority to nitrofurantoin in the treatment of uUTI in this patient population. In total, the study enrolled 541 patients who were randomly assigned to receive 1500 mg gepotidacin BID (n = 277) or to 100 mg nitrofurantoin BID (n = 264).

In that trial, therapeutic success was achieved in 58.5% of patients in the gepotidacin arm vs 43.6% of patients in the nitrofurantoin arm (treatment difference, 14.6%; 95% CI, 6.4% to 22.8%). Clinical success, defined as symptom resolution at the test of cure visit, was achieved in 67.9% of patients in the gepotidacin arm vs 63.3% of patients in the nitrofurantoin arm (treatment difference, 4.4%; 95% CI, -3.5% to 12.3%). Further, 72.2% of patients in the gepotidacin arm and 57.2% of patients in the nitrofurantoin arm achieved microbiological success, defined as the eradication of qualifying uropathogen to less than 10³ CFU/mL (treatment difference, 15.0%; 95% CI, 7.2% to 22.9%).

Across both studies, the safety and tolerability profile for gepotidacin was consistent with previously reported data. Gastrointestinal complaints were the most common adverse events (AEs) reported, which included diarrhea in 16% of patients and nausea in 9% of patients. The majority of gastrointestinal AEs were mild, with 69% being grade 1 and 28% being grade 2. There was 1 drug-related serious adverse event in each treatment arm.

In both studies, the trial duration for all participants was approximately 28 days. The primary end point was the composite clinical and microbiological response at the test of cure visit (conducted on days 10 to 13) in patients with qualifying uropathogens susceptible to nitrofurantoin.

REFERENCES
1. Blujepa (gepotidacin) approved by US FDA for treatment of uncomplicated urinary tract infections (uUTIs) in female adults and paediatric patients 12 years of age and older. News release. GSK. Published online and accessed March 25, 2025. https://www.gsk.com/en-gb/media/press-releases/blujepa-gepotidacin-approved-by-us-fda-for-treatment-of-uncomplicated-urinary-tract-infections/

2. 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 March 25, 2025. 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/

3. Gepotidacin’s positive phase III data shows potential to be the first in a new class of oral antibiotics for uncomplicated urinary tract infections in over 20 years. News release. GSK. April 15, 2023. Accessed March 25, 2025. https://www.gsk.com/en-gb/media/press-releases/gepotidacin-s-positive-phase-iii-data-shows-potential-to-be-the-first-in-a-new-class-of-oral-antibiotics-for-uncomplicated-urinary-tract-infections/