The FDA has approved gepotidacin, marketed as Blujepa, as a first-in-class oral antibiotic for the treatment of uncomplicated urinary tract infections in female adults and pediatric patients aged 12 years or older and weighing at least 88.2 pounds. Gepotidacin is a triazaacenaphthylene bacterial type II topoisomerase inhibitor, representing a novel chemical class, and is the first oral antibiotic with a new mechanism of action approved for uncomplicated urinary tract infections in nearly 30 years.

Approval was based on data from two randomized, double-blind, active-controlled phase III trials (EAGLE-2 and EAGLE-3) conducted by researchers at GSK. Gepotidacin demonstrated in vitro activity against common uropathogens, including Escherichia coli and Staphylococcus saprophyticus, which are responsible for most uUTIs, including some drug-resistant strains.

EAGLE-2 and EAGLE-3 enrolled 1,531 and 1,605 participants, respectively, to evaluate gepotidacin (1,500 mg orally twice daily for 5 days) compared with nitrofurantoin (100 mg orally twice daily for 5 days) in female patients with culture-confirmed uncomplicated urinary tract infections (uUTIs) caused by nitrofurantoin-susceptible pathogens. The primary endpoint was therapeutic success, defined as a composite of clinical resolution and microbiological eradication, assessed at the test-of-cure visit (days 10–13).

In EAGLE-2, gepotidacin achieved therapeutic success in 50.6% (162 of 320) of patients versus 47.0% (135 of 287) for nitrofurantoin, with a covariate-adjusted treatment difference of 4.3% (95% CI, −3.6 to 12.1), meeting the noninferiority margin. In EAGLE-3, gepotidacin demonstrated superiority, with therapeutic success in 58.5% (162 of 277) compared with 43.6% (115 of 264) for nitrofurantoin, for a treatment difference of 14.6% (95% CI, 6.4–22.8; one-sided P = .0003).

The safety profile of gepotidacin was consistent with prior studies. The most common adverse events were gastrointestinal, including diarrhea (16%) and nausea (9%). Most events were mild (69% grade 1) or moderate (28% grade 2); fewer than 1% were grade 3. One drug-related serious adverse event occurred in each treatment arm across both trials.

A U.S. commercial launch is anticipated in the second half of 2025.

Reference

GSK. 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 [press release].