FDA Approves Gepotidacin (Blujepa) for Treatment of Uncomplicated UTIs

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The US FDA today approved gepotidacin (Blujepa; GSK) for the treatment of uncomplicated urinary tract infections (uUTIs) in female patients aged 12 and older. This approval marks the first new class of oral antibiotics for uUTIs in nearly 30 years.¹

Gepotidacin is a bactericidal, first-in-class triazaacenaphthylene antibiotic that inhibits bacterial DNA replication by targeting two different Type II topoisomerase enzymes. The drug is indicated for uUTIs caused by susceptible strains of Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii complex, Staphylococcus saprophyticus, and Enterococcus faecalis.¹

More than half of all women experience a uUTI in their lifetime, with approximately 30% developing recurrent infections, leading to significant patient burden, including discomfort and limitations in daily activities.^2,3 The growing number of uUTIs due to drug-resistant bacteria further underscores the need for new treatment options.⁴

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

The approval is based on results from the pivotal phase 3 EAGLE-2 and EAGLE-3 clinical trials. In EAGLE-2, gepotidacin demonstrated non-inferiority to nitrofurantoin, with a therapeutic success rate of 50.6% compared to 47.0% for nitrofurantoin (covariate-adjusted treatment difference 4.3%, 95% CI [-3.6, 12.1]). In EAGLE-3, gepotidacin showed statistically significant superiority over nitrofurantoin, with therapeutic success in 58.5% of participants compared to 43.6% for nitrofurantoin (covariate-adjusted treatment difference 14.6%, 95% CI [6.4, 22.8], P = 0.0003).¹

“The approval of [gepotidacin] is a crucial milestone with uUTIs among the most common infections in women,” Tony Wood, Chief Scientific Officer, GSK, said in the press release.¹ We are proud to have developed [gepotidacin], 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.”

The safety profile of gepotidacin in phase 3 trials was consistent with previous studies. The most commonly reported adverse events were gastrointestinal-related, with diarrhea occurring in 16% of participants and nausea in 9%. The majority of these adverse events were mild (69% Grade 1) or moderate (28% Grade 2), with Grade 3 events occurring in <1% of participants. One drug-related serious adverse event was reported in each treatment arm (gepotidacin and nitrofurantoin).¹

GSK plans to commercially launch gepotidacin in the US in the second half of 2025. The drug's development was partially funded by the US Department of Health and Human Services' Biomedical Advanced Research and Development Authority (BARDA) and the Defense Threat Reduction Agency.¹

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. 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. Czajkowski K, Broś-Konopielko M, Teliga-Czajkowska J. Urinary tract infection in women. Prz Menopauzalny. 2021;20:40-47. doi:10.5114/pm.2021.105382

3. Little P, Merriman R, Turner S, et al. Presentation, pattern, and natural course of severe symptoms, and role of antibiotics and antibiotic resistance among patients presenting with suspected uncomplicated urinary tract infection in primary care: Observational study. BMJ. 2010;340:b5633. doi:10.1136/bmj.b5633

4. Kaye KS, Gupta V, Mulgirigama A, et al. Antimicrobial resistance trends in urine Escherichia coli isolates from adult and adolescent females in the United States from 2011 to 2019: Rising ESBL strains and impact on patient management. Clin Infect Dis 2021;73:1992–1999. doi:10.1093/cid/ciab560