Single-Arm Gepotidacin Trial Reports UTI Symptom Resolution Within 24 Hours

More than half of females with uncomplicated urinary tract infections (uUTIs) treated with oral gepotidacin had symptom improvement within 24 hours of starting therapy, according to a phase 3b nonrandomized clinical trial published in JAMA Network Open.

Gepotidacin is a first-in-class triazaacenaphthylene oral antibacterial that inhibits bacterial DNA replication. The FDA approved it in March 2025 for female adult and pediatric patients 12 years or older weighing 40 kg or more with uUTIs caused by susceptible Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii complex, Staphylococcus saprophyticus, and Enterococcus faecalis. The investigators noted that the pivotal EAGLE-2 and EAGLE-3 trials first assessed symptoms at days 2 to 4 and that few studies have evaluated symptom response within the first 24 hours of treatment.

The open-label, single-arm trial (NCT06597344) enrolled 97 females at 21 US sites, who received gepotidacin 1500mg twice daily for 5 days. The primary outcome was clinical symptom improvement, defined as a decrease of at least 1 point in total clinical symptom score from baseline without other systemic antimicrobials, at 24 hours. Among 90 clinically evaluable participants, 49 (54.4%; 95% CI, 43.6%-65.0%) met the primary outcome. Improvement was reported in 79.8% of participants at 48 hours and 95.6% at day 10, while complete symptom resolution rose from 3.3% at 24 hours to 90.0% at day 10.

Overall, 27 of 97 participants (28%) reported 58 adverse events (AEs), most of them mild or moderate, and no serious AEs occurred. Diarrhea was the most common AE (16%), with 2 severe cases. Three participants (3%) discontinued treatment because of drug-related AEs. No Clostridioides difficile–associated diarrhea or QT prolongation was reported.

The authors cited the open-label, single-arm design, small sample size, and descriptive-only analysis as limitations, and noted that a high proportion of Hispanic or Latinx participants and few women 65 years or older may limit generalizability. The study was funded by GSK, and 7 of the 8 authors reported being GSK employees.

Source: Ramírez M, Gupta K, Díaz-Regañón J, et al. Gepotidacin and early symptom improvement in uncomplicated urinary tract infection: a nonrandomized clinical trial. JAMA Netw Open. 2026;9(9):e2634116. doi:10.1001/jamanetworkopen.2026.34116