FDA Approves Gepotidacin (Blujepa) for Uncomplicated UTI

The US Food and Drug Administration has approved GSK’s gepotidacin (Blujepa) for the treatment of uncomplicated urinary tract infections (uUTIs) caused by Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii complex, Staphylococcus saprophyticus and Enterococcus faecalis in female adults weighing ≥40 kg and adolescents ≥12 years of age weighing ≥40 kg.1

Announced on March 25, 2025, the decision is supported by positive results from the phase 3 Efficacy of Antibacterial Gepotidacin Evaluated (EAGLE)-2 and EAGLE-3 trials, where gepotidacin demonstrated non-inferiority to nitrofurantoin, the current standard of care for uUTI, in female adults and adolescents with a confirmed uUTI and a uropathogen susceptible to nitrofurantoin. According to GSK, US commercial launch is planned in 2H 2025.11

“For many, uUTIs can be a burden that severely impacts daily life. 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,” said Thomas Hooton, MD, a professor of clinical medicine at the University of Miami School of Medicine.1

An investigational bactericidal, first-in-class triazaacenaphthylene antibiotic, gepotidacin inhibits bacterial DNA replication by a distinct binding site, a novel mechanism of action, and for most pathogens, facilitates well-balanced inhibition of 2 different Type II topoisomerase enzymes, providing activity against most target uropathogens (such as E. coli and S. saprophyticus), and N. gonorrhoeae, including isolates resistant to current antibiotics.2

EAGLE-2 and EAGLE-3 compared the efficacy and safety of gepotidacin 1500 mg administered orally twice daily for 5 days to nitrofurantoin 100 mg administered orally twice daily for 5 days in 1531 and 1605 female adults and adolescents with uncomplicated urinary tract infections, respectively. The primary endpoint was the combined clinical and microbiological response at the Test-of-Cure (ToC) visit at days 10-13 in patients with qualifying uropathogens susceptible to nitrofurantoin.2

In EAGLE-3, gepotidacin achieved statistically significant superiority versus nitrofurantoin, demonstrating therapeutic success in 58.5% of participants compared to 43.6% for nitrofurantoin (treatment difference, 14.6%; 95% CI, 6.4 to 22.8). In EAGLE-2, gepotidacin demonstrated therapeutic success in 50.6% of participants compared to 47.0% for nitrofurantoin (treatment difference, 4.3%; 95% CI, -3.6 to 12.1).2

The safety and tolerability of gepotidacin in the EAGLE-2 and EAGLE-3 trials were consistent with previous trials of gepotidacin. The most commonly reported adverse events in gepotidacin participants were gastrointestinal, with diarrhea (16%) and nausea (9%) being the most common.2

“The approval of Blujepa is a crucial milestone with uUTIs among the most common infections in women,” said Tony Wood, Chief Scientific Officer of GSK.1 “We are proud to have developed Blujepa, the first in a new class of oral antibiotics for uUTIs in nearly three decades, and to bring another option to patients given recurrent infections and rising rates of resistance to existing treatments.”

References

1. 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. March 25, 2025. 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. GSK. Gepotidacin accepted for priority review by US FDA for treatment of uncomplicated urinary tract infections in female adults and adolescents. October 16, 2024. Accessed March 24, 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/