The US Food and Drug Administration (FDA) has received a supplemental New Drug Application for gepotidacin requesting priority review. The application is requesting to approve gepotidacin as an orally administered therapy of uncomplicated urogenital gonorrhea in patients aged 12 years and above with a weight of at least 45 kg. The FDA action date under the Prescription Drug User Fee Act (PDUFA) is December 11, 2025.
In March 2025, Gepotidacin was approved in the United States under the brand name Blujepa to treat uncomplicated urinary tract infections (uUTIs) in female adults and children aged 12 years and older weighing≥40 kg. The approved dosage for uUTI is 1,500 mg orally twice daily for 5 days.
Gepotidacin, invented by GSK researchers, is a triazaacenaphthylene-based first-in-class antibiotic. It acts by inhibiting bacterial DNA replication at a specific binding site and targets two Type II topoisomerase enzymes. This makes it active against Neisseria gonorrhoeae and common uropathogens like Escherichia coli and Staphylococcus saprophyticus, including resistant strains. Its mechanism implies that a single mutation will not significantly reduce its functionality.
Gonorrhea, a serious sexually transmitted infection, is caused by the bacterium Neisseria gonorrhoeae, which the World Health Organization (WHO) lists as a priority pathogen and the US CDC identifies as an urgent public health threat. Men and women can be infected, and unless it is treated, the infection may cause infertility and other complications related to reproductive health. In 2023, gonorrhea became the second most reported sexually transmitted infection in the US, and the CDC reported more than 600,000 cases.
The US is now lacking an approved gonorrhea vaccine, and the conventional treatment is based on injectables, which are inappropriate and inaccessible to all. The EAGLE-1 phase III trial results, published in The Lancet, support the FDA review. The research revealed that gepotidacin (two 3,000 mg orally) was non-inferior to the usual one combination of 500 mg ceftriaxone (intramuscular) and 1,000 mg azithromycin (oral).
Gepotidacin showed a 92.6% (187/202, 95% CI: 88.0 to 95.8) success rate at the urogenital site, compared with 91.2% (186/204, 95% CI: 86.4 to 94.7) achieved with the standard therapy.
Neither group had treatment failures due to persistent N. gonorrhoeae. The safety results were consistent with prior research, and there were no severe adverse drug reactions. Gastrointestinal problems (primarily Grade 1 or Grade 2) were the most frequent side effects. This is the second large US filing of gepotidacin. The uUTI indication is also being reviewed in terms of regulation in the UK and Australia. The global phase III study will have three large clinical trials.
Non-inferiority EAGLE-1 is a trial of gepotidacin in uncomplicated urogenital gonorrhea in approximately 600 participants, the results of which were reported at ESCMID in April 2024 and published in April 2025. EAGLE-2 and EAGLE-3 are uncomplicated urinary tract infection (uUTI) non-inferiority trials, pitting 1,500 mg of gepotidacin orally twice a day for 5 days against 100 mg of nitrofurantoin orally twice a day for 5 days. The results of these two trials were initially reported at ECCMID in 2023.
References: GSK. Gepotidacin accepted for priority review by the US FDA for the oral treatment of uncomplicated urogenital gonorrhea. Published December 11, 2025. Accessed December 12, 2025. Gepotidacin accepted for priority review by the US FDA for the oral treatment of uncomplicated urogenital gonorrhea
