A NOVEL oral antibiotic, gepotidacin, has shown comparable effectiveness to current first-line therapy for uncomplicated urogenital gonorrhoea, according to results from the EAGLE-1 phase 3 clinical trial published this week.
Gepotidacin, a first-in-class antibacterial that inhibits bacterial DNA replication, achieved a microbiological cure rate of 92.6%, closely matching the 91.2% success rate of standard treatment with intramuscular ceftriaxone plus oral azithromycin. The trial met its primary endpoint for non-inferiority, suggesting gepotidacin could serve as a viable oral alternative.
The study enrolled 628 participants aged 12 years and older with suspected or confirmed urogenital gonorrhoea. Most were male (92%) and a majority identified as men who have sex with men (MSM). Participants were randomly assigned to receive either two doses of oral gepotidacin or the standard injectable/oral combination therapy.
Importantly, no cases of persistent gonorrhoea were observed in either treatment group. While gepotidacin was associated with a higher rate of mild-to-moderate gastrointestinal side effects, no serious treatment-related adverse events occurred.
The findings arrive at a critical time as antibiotic resistance in Neisseria gonorrhoeae continues to threaten current treatment regimens. Oral gepotidacin offers a convenient and potentially more accessible option, especially in settings where injections are impractical or poorly tolerated.
Researchers noted that continued surveillance and further studies will be necessary to monitor resistance and long-term efficacy, but the results mark an important milestone in the development of next-generation gonorrhoea therapies.
Aleksandra Zurowska, EMJ
Reference
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. Lancet. 2025;DOI: 10.1016/S0140-6736(25)00628-2.
