Trial enrollment for uUTI drug stopped early after primary outcome for efficacy was reached

"There has been no new class of oral antibiotics for uUTI for over 20 years," says Chris Corsico.

Phase 3 trials evaluating gepotidacin for the treatment of uncomplicated urinary tract infection (uUTI) have stopped enrollment early after efficacy data showed primary end points being met.¹

The recommendation to do so was issued by the Independent Data Monitoring Committee (IDMC) following their pre-specified interim analysis of the trial data, according to a news release by GSK. Gepotidacin is an investigational oral antibiotic treatment developed for uUTI in female adults and adolescents.

“Uncomplicated urinary tract infections (uUTI) are the most common outpatient infection with over half of all women developing a uUTI during their lifetime and more than a quarter of women suffering from recurrent uUTIs. There has been no new class of oral antibiotics for uUTI for over 20 years. With the number of uUTIs caused by resistance bacteria increasing, new antibiotic treatments are necessary. The IDMC’s recommendation to stop the EAGLE-2 and 3 trials early for efficacy provides GSK with the opportunity to engage regulatory authorities as we work together to bring a new class of antibiotics to patients with uUTIs,” said Chris Corsico, SVP of Development at GSK.

Gepotidacin was developed through a partnership with GSK and the US government’s Biomedical Advanced Research and Development Authority (BARDA). The collaboration was established in 2013 in an effort to develop antibiotics to fight antibiotic resistance and bioterrorism.

Responses to gepotidacin were analyzed in comparison to nitrofurantoin in the phase 3 EAGLE-2 and 3 trials, which included patient data from over 3000 participants across the studies. Patients selected for participation needed to have a confirmed uUTI and a uropathogen sensitive to nitrofurantoin.

Data collected looked specifically at efficacy and safety outcomes in gepotidacin (1500mg administered orally twice daily for 5 days) vs nitrofurantoin (100 mg administered orally twice daily for 5 days). The primary end point for both studies was combined clinical and microbiological resolution following treatment at the Test-Of-Cure visit in patients with uUTIs and qualifying uropathogens. Both trials were similar, but EAGLE-2 provided additional pharmacokinectic data and EAGLE-3 included an on-treatment ECG test.

Recruitment for the studies is now closed, and final study visits and data collections are expected during the first quarter of 2023. Enrollment was closed after the data analysis by IDMC, which determined that the primary efficacy outcome of clinical and microbiological resolution following treatment was met.

“The IDMC review did not identify any safety concerns,” GSK reported in the release.

The full results from the studies are expected to be submitted for presentation at a scientific congress and for publication in a peer-reviewed journal in 2023.

Reference

1. EAGLE-2 and EAGLE-3 phase III trials for gepotidacin stopped early for efficacy following pre-planned interim analysis by Independent Data Monitoring Committee. News release. GSK. November 3, 2022. Accessed November 4, 2022. https://www.gsk.com/en-gb/media/press-releases/gsk-announces-phase-iii-trials-for-gepotidacin/