FDA accepts gepotidacin for priority review for gonorrhea oral treatment

FDA accepts priority review for gepotidacin as oral treatment for gonorrhea | Image credit Contemporary OB/GYN

The FDA has accepted for priority review a supplemental New Drug Application (sNDA) for gepotidacin (Blujepa; GSK) as an oral treatment option for uncomplicated urogenital gonorrhea in patients aged 12 years and older weighing at least 45 kg, according to GSK. The Prescription Drug User Fee Act action date is December 11, 2025.¹

Recently, gepotidacin received FDA approval in March 2025 as an oral treatment for uncomplicated urinary tract infections (uUTI) in female adult and pediatric patients aged 12 years and older weighing at least 40 kg. Regulatory review for the uUTI indication is also underway in the United Kingdom and Australia.

In 2023, more than 600,000 US cases were reported, making gonorrhea the second most frequently reported STI in the country. If untreated or inadequately treated, infection can result in infertility and other reproductive health complications. There is currently no licensed vaccine in the United States, and standard treatment involves injectable therapy, which may be unsuitable or unavailable for some patients.¹

The sNDA is supported by findings from the phase 3 EAGLE-1 trial, published in The Lancet, which evaluated gepotidacin as a non-inferior oral alternative to the current leading treatment combination of intramuscular ceftriaxone and oral azithromycin. EAGLE-1 enrolled participants aged 12 years and older with suspected uncomplicated urogenital gonorrhea. Participants were randomly assigned to receive either gepotidacin (two oral doses of 3000 mg administered 10–12 hours apart) or ceftriaxone (500 mg intramuscular) plus azithromycin (1 g oral).²

The primary endpoint was microbiological success at test-of-cure (days 4–8), defined as culture-confirmed eradication of N gonorrhoeae from the urogenital site. In the microbiological intention-to-treat population (n=406), microbiological success was achieved in 92.6% (187/202; 95% CI, 88.0–95.8) of patients receiving gepotidacin and 91.2% (186/204; 95% CI, 86.4–94.7) receiving ceftriaxone plus azithromycin, meeting the non-inferiority margin. No bacterial persistence at the urogenital site was reported in either treatment group.

Gepotidacin demonstrated a safety and tolerability profile consistent with prior clinical studies. The most common adverse events were gastrointestinal, primarily mild to moderate in severity. “No treatment-related severe or serious adverse events occurred in either group,” the investigators reported.

GSK noted that this is the second major US regulatory submission for gepotidacin. “The FDA’s acceptance of our application for priority review reflects the potential of gepotidacin to address a significant unmet need in gonorrhea treatment,” the company stated.

Gepotidacin is a bactericidal, first-in-class triazaacenaphthylene antibiotic. It inhibits bacterial DNA replication through a novel mechanism of action involving a distinct binding site and, for most pathogens, balanced inhibition of 2 different type II topoisomerase enzymes. This mechanism provides activity against N gonorrhoeae and most target uropathogens, including Escherichia coli and Staphylococcus saprophyticus, even in strains resistant to current antibiotics.

If approved, gepotidacin would represent the first oral treatment option for uncomplicated urogenital gonorrhea in the United States and could reduce reliance on injectable regimens, potentially improving access to care and adherence.

References:

1. GSL. Gepotidacin accepted for priority review by the US FDA for the oral treatment of uncomplicated urogenital gonorrhoea. GSK. August 11, 2025. Accessed August 12, 2025. https://www.gsk.com/en-gb/media/press-releases/gepotidacin-accepted-for-priority-review-by-the-us-fda-for-the-oral-treatment-of-uncomplicated-urogenital-gonorrhoea/
2. Ross JDC, Wilson J, Workowski KA, et al. Oral gepotidacin for the treatment of uncomplicated urogenital gonorrhoea (EAGLE-1): a phase 3 randomised, open-label, non-inferiority, multicentre study. The Lancet. Published online April 2025. doi:https://doi.org/10.1016/s0140-6736(25)00628-2