TOPLINE

Oral gepotidacin demonstrated high treatment success rates for uncomplicated urogenital gonorrhea, with nucleic acid amplification test (NAAT)-confirmed success rates similar to those of ceftriaxone plus azithromycin. Baseline concordance between NAAT and culture results was high at 98.4%, supporting NAAT as a complementary diagnostic tool in future gonorrhea clinical trials.

METHODOLOGY

• Researchers conducted a phase 3, open-label, multicenter, active comparator-controlled, noninferiority study to compare the efficacy and safety of oral gepotidacin with those of intramuscular ceftriaxone plus oral azithromycin for treating patients with uncomplicated urogenital gonorrhea.
• They enrolled 628 participants aged 12 years or older and weighing more than 45 kg with clinical suspicion of urogenital gonococcal infection; of these, 406 participants (mean age, 33.1 years) with culture-confirmed ceftriaxone-susceptible urogenital Neisseria gonorrhoeae at baseline were included in the microbiologic intent-to-treat (micro-ITT) population.
• Participants received either oral gepotidacin (two 3000-mg doses administered 10-12 hours apart) or intramuscular ceftriaxone (500 mg) plus oral azithromycin (1 g), each as single doses; urogenital specimens were collected at baseline and at the test-of-cure visits (days 4-8) for the NAAT assay.
• The primary efficacy endpoint was microbiologic success, defined as the culture-confirmed eradication of N gonorrhoeae from the urogenital body site at the test-of-cure visit. This exploratory analysis assessed microbiologic success using the NAAT assay.
• The microbiologically evaluable NAAT test-of-cure population comprised 324 participants (171 received gepotidacin and 153 received ceftriaxone plus azithromycin) who met specific protocol criteria and had valid baseline NAAT-positive and test-of-cure NAAT results.

TAKEAWAY

• In the micro-ITT population, NAAT-confirmed treatment success rates at the test-of-cure visits were 82.5% (151 of 183) for gepotidacin and 75.0% (132 of 176) for ceftriaxone plus azithromycin (adjusted difference, 8.2%; 95% CI, -0.1% to 16.5%).
• In the microbiologically evaluable NAAT test-of-cure population, treatment success rates were 88.3% (151 of 171) for gepotidacin and 86.3% (132 of 153) for ceftriaxone plus azithromycin (adjusted difference, 3.8%; 95% CI, -3.6% to 11.2%).
• In the microbiologically evaluable NAAT test-of-cure population, NAAT failures for urogenital N gonorrhoeae were mainly due to nucleic acid persistence, which occurred at similar rates with gepotidacin (11.7%) and ceftriaxone plus azithromycin (13.7%).
• For N gonorrhoeae specimens collected from rectal sites, NAAT success numerically favored gepotidacin, whereas for N gonorrhoeae specimens collected from pharyngeal sites, NAAT success numerically favored ceftriaxone plus azithromycin.
• Baseline concordance between central laboratory NAAT and culture results for urogenital N gonorrhoeae was 98.4%, with a sensitivity of 99.4% and a positive predictive value of 98.9%.

IN PRACTICE

“[T]reatment success rates determined by NAAT at the urogenital site were high and similar following treatment with gepotidacin or ceftriaxone plus azithromycin, supporting the primary analysis based on culture,” the authors wrote. “With similar efficacy conclusions between NAAT and culture, NAAT may be a promising addition to culture in future registrational urogenital gonorrhea clinical trials, offering rapid testing with greater practicality and diagnostic sensitivity to complement the antimicrobial susceptibility profiling provided by culture,” they concluded.

SOURCE

The study was led by William G. Flight, MD, PhD, GSK, London, England. It was published online on July 17, 2026, in Open Forum Infectious Diseases.

LIMITATIONS

The timing of test-of-cure evaluation favored culture-based assessment over the NAAT assay. Efficacy results for rectal and pharyngeal N gonorrhoeae were derived from few specimens, so findings at these nonurogenital sites should be interpreted cautiously. The trial enrolled only participants with ceftriaxone-susceptible isolates, so further study is needed to assess gepotidacin in ceftriaxone-resistant gonorrhea.

DISCLOSURES

This study was supported in part by GSK and in part with federal funds from the Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority. Seven authors declared being employed by GSK and holding financial equities in GSK. Some authors reported receiving consultancy fees from GSK Pharma or having ownership of shares in GSK Pharma, AstraZeneca Pharma, or Organon LLC. Full disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.