TOPLINE

In a phase 3b trial, gepotidacin, a first-in-class oral antibacterial, improved uncomplicated urinary tract infection (uUTI) symptoms in more than half of clinically evaluable female participants within 24 hours of treatment initiation. Symptom improvement occurred in 90% of participants by 72 hours, and complete symptom resolution was reported in 90% of participants by day 10.

METHODOLOGY

• Researchers conducted a phase 3b, open-label, single-arm, multicenter, nonrandomized clinical trial to assess clinical symptom improvement during treatment with gepotidacin in women with uUTI between October 2024 and March 2025.
• They enrolled 97 females aged 12 years or older (mean age, 45.7 years) with two or more uUTI symptoms plus urinary nitrites or pyuria who received oral gepotidacin 1500 mg twice daily for 5 days.
• Clinical symptom scores (CSS, range 0-12) were assessed via telephonic interviews at 24, 48, 72, and 96 (all ± 4) hours and again at day 10.
• Researchers assessed the primary outcome of clinical symptom improvement (CSS decrease ≥ 1 from baseline) at 24 hours (± 4 hours) after treatment initiation in 90 clinically evaluable participants.
• Secondary outcomes were clinical symptom improvement at 48, 72, and 96 hours after treatment began, clinical symptom resolution (a reduction in total CSS to 0 at 24, 48, 72, and 96 hours), as well as safety and tolerability.

TAKEAWAY

• Overall, clinical symptom improvement (with or without resolution) occurred in 54.4% (49/90) of clinically evaluable participants at 24 hours; the proportion rose to 79.8% (71/89) at 48 hours and 90.0% (81/90) at 72 hours, before dipping to 86.5% (77/89) at 96 hours and again rising to 95.6% (86 of 90) by day 10.
• The proportion of participants achieving complete symptom resolution rose over time, from 3.3% (3/90) at 24 hours to 53.9% (48/89) at 96 hours and 90.0% (81/90) by day 10. None of the participants required additional nonstudy antimicrobials through day 10, indicating that efficacy outcomes were not confounded by rescue therapy. 
• Mean CSS for both individual symptoms (dysuria, frequency, urgency, and lower abdominal or suprapubic pain) and total CSS declined by 24 hours after treatment initiation and continued to decrease over time through day 10, with a corresponding rise in the proportion of participants reporting no symptoms at all.
• Among the safety population (n = 97), 27 participants (28%) experienced 58 adverse events (AEs); most of them had mild (74%) or moderate AEs (19%), with diarrhea being the most common AE. Of the 97 participants, 25% experienced study drug-related AEs, and 3% discontinued treatment due to drug-related AEs.

IN PRACTICE

"Together these findings support gepotidacin as an option to address the unmet need for new oral antibacterials in uUTI treatment and provide a basis for more informed discussions between patients and clinicians regarding treatment expectations," the authors concluded.

SOURCE

The study was led by Marcela Ramírez, MD, of GSK in London, England. It was published online on September 29 in JAMA Network Open.

LIMITATIONS

The study's open-label, single-arm design and small sample size constrained the generalizability of its findings. The enrolled population had a disproportionately high share of Hispanic or Latinx individuals and a small share of women aged 65 years or older, which further limited generalizability.

DISCLOSURES

The study was funded by GSK. Seven authors declared being employees of GSK, and six of them declared being stockholders in the company. Another author reported consulting for GSK and several other companies. Full disclosures are reported 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.