FDA Approves GSK’s Gepotidacin for Gonorrhea

Today, the FDA approved GSK’s antibiotic, gepotidacin, for the treatment of uncomplicated urogenital gonorrhea in patients 12 years or older (weighing ≥ 45 kg [99.2 lb]). This approval was based from data of the EAGLE-1 phase 3 trial results, which were published in The Lancet, showing that gepotidacin (oral, 2 doses of 3000 mg) was noninferior, with a 92.6% (187 of 202; 95% CI, 88.0%-95.8%) success rate at urogenital site when compared with a 91.2% (186 of 204; 95% CI, 86.4%-94.7%) success rate for intramuscular ceftriaxone (500 mg) plus oral azithromycin (1000 mg) combined therapy.¹

This approval provides a new oral option for this sexually transmitted infection (STI) becomes available.

“We’re proud to have delivered the first new class of antibiotics for gonorrhea in over three decades and a new oral option for US patients. The ability of N gonorrhoeae to develop resistance to currently available options, including standard of care, makes it important to expand the range of effective oral treatments,” GSK Chief Scientific Officer Tony Wood, PhD, said in a statement.²

“Gepotidacin demonstrated noninferiority to ceftriaxone plus azithromycin for urogenital N gonorrhoeae, with no new safety concerns, offering a novel oral treatment option for uncomplicated urogenital gonorrhea,” The Lancet wrote.¹

The Study Specifics and Results

The EAGLE-1 study was an open-label noninferiority trial examining oral gepotidacin compared with ceftriaxone plus azithromycin. Participants had to have a body weight over 45 kg, and had suspected uncomplicated urogenital gonorrhea (including mucopurulent discharge), a positive laboratory test result for Neisseria gonorrhoeae, or both. Patients were randomly allocated in a 1:1 ratio to each treatment group, stratified by sex and sexual orientation.¹

The primary efficacy end point was defined as eradication of gonorrhea at test of cure (days 4-8). The noninferiority margin was prespecified at –10%. The primary outcome was assessed in the microbiological intention-to-treat population, with all participants randomly allocated to a study treatment who received at least 1 dose of their treatment and had confirmed ceftriaxone-susceptible N gonorrhoeae isolated from the baseline culture of their urogenital specimen, The Lancet authors explained.¹

About the Agent

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 2 different Type II topoisomerase enzymes. This provides activity against Neisseria gonorrhoeae and most target uropathogens (such as Escherichia coli and Staphylococcus saprophyticus), including isolates resistant to current antibiotics. Due to this well-balanced inhibition for most pathogens, a single target-specific mutation may not significantly impact gepotidacin activity.

Other Approval

This is the second major indication filed in the US for gepotidacin. The antibiotic was  FDA approved back in March for uncomplicated urinary tract infections (uUTIs).³

References

1. Ross JDC, Wilson J, Workowski KA, et al. Oral gepotidacin for the treatment of uncomplicated urogenital gonorrhea (EAGLE-1): a phase 3 randomised, open-label, non-inferiority, multicentre study. Lancet. 2025;405(10489):1608-1620. doi:10.1016/S0140-6736(25)00628-2

2. Blujepa (gepotidacin) approved by US FDA as oral option for treatment of uncomplicated urogenital gonorrhoea (uGC) GSK Press release. December 11, 2025. Accessed December 11, 2025.

3. Parkinson J. Newly FDA-approved UTI antibiotic shows high efficacy for gonorrhea treatment. Contagion. April 15, 2025. Accessed August 12, 2025.
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