Gepotidacin demonstrates efficacy, safety as treatment for gonorrhea

Gepotidacin demonstrates effectiveness against gonorrhea | Image Credit: © NurJahan - stock.adobe.com.

A novel oral antibiotic, gepotidacin (Blujepa; GSK), has demonstrated its effectiveness in treating uncomplicated urogenital gonorrhea, according to the results of a recent phase 3 clinical trial.¹

The phase 3, open-label, sponsor-blinded, multicentre, non-inferiority study, EAGLE-1, compared gepotidacin to intramuscular ceftriaxone plus oral azithromycin for the treatment of gonorrhea. The trial was conducted across various locations and enrolled 628 participants aged 12 years and older who were suspected of having uncomplicated urogenital gonorrhea.

Participants either presented with symptoms such as mucopurulent discharge or had a positive laboratory test for N. gonorrhoeae. They were randomly assigned to receive either 2, 3000-mg doses of oral gepotidacin taken 10 to 12 hours apart, or a single 500-mg intramuscular injection of ceftriaxone along with a single 1-g oral dose of azithromycin.

The primary goal of the study was to determine if gepotidacin was as effective as the standard treatment in achieving microbiological success, defined as the absence of N. gonorrhoeae in urogenital cultures taken 4 to 8 days after treatment. This analysis focused on the "microbiological intention-to-treat" (micro-ITT) population, which included 406 participants who received at least 1 dose of their assigned treatment and whose initial gonorrhea samples were susceptible to ceftriaxone.

The results of the primary analysis showed high rates of bacterial eradication in both treatment groups. In the gepotidacin group, 92.6% (187 out of 202 participants) achieved microbiological success, while the ceftriaxone plus azithromycin group had a success rate of 91.2% (186 out of 204 participants). Statistical analysis revealed that gepotidacin was non-inferior to the standard treatment, with an adjusted treatment difference of -0.1% (95% Confidence Interval: -5.6% to 5.5%). Notably, no instances of persistent N. gonorrhoeae infection were detected in either group at the follow-up visit.

The study also assessed the safety and tolerability of gepotidacin. While the gepotidacin group experienced a higher rate of adverse events, these were predominantly mild to moderate gastrointestinal issues such as nausea, vomiting, or diarrhea. Importantly, there were no treatment-related severe or serious adverse events reported in either treatment arm. Premature discontinuation from the study occurred in 39 participants (20 in the gepotidacin group and 19 in the ceftriaxone plus azithromycin group), primarily due to participants being lost to follow-up.

The researchers concluded that gepotidacin demonstrated comparable effectiveness to the current standard treatment for uncomplicated urogenital gonorrhea. The oral administration of gepotidacin offers a potentially more convenient treatment option for patients. The safety profile, while showing a higher incidence of mild gastrointestinal side effects, did not raise any new safety concerns.

These findings are significant as they introduce a novel class of antibacterial drug, a triazaacenaphthylene that works by inhibiting bacterial DNA replication, into the gonorrhea treatment landscape.

While further research may be warranted, the authors concluded, "Gepotidacin demonstrated non-inferiority to ceftriaxone plus azithromycin for urogenital N gonorrhoeae, with no new safety concerns, offering a novel oral treatment option for uncomplicated urogenital gonorrhoea."

In March 2025, gepotidacin was approved to treat uncomplicated urinary tract infections in female patients 12 years and older.²

GSK said they plan to file for FDA approval of geptidacin for the treatment of gonorrhea later this year.

References:

1. Ross J, 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. April 14, 2025. Accessed April 15, 2025. doi: 10.1016/S0140-6736(25)00628-2

2. Blujepa (gepotidacin) approved by US FDA for treatment of uncomplicated urinary tract infections (uUTIs) in female adults and pediatric patients 12 years of age and older. GSK. March 25, 2025. Accessed April 15, 2025.
https://www.gsk.com/en-gb/media/press-releases/blujepa-gepotidacin-approved-by-us-fda-for-treatment-of-uncomplicated-urinary-tract-infections/