An Independent Data Monitoring Committee recommends stopping 2 phase 3 trials early for efficacy following positive results in November 2022.
Gepotidacin, an investigational oral antibiotic, for uncomplicated urinary tract infections (uUTIs) in female adolescents and adults, shows potential to be a new first-in-class drug for oral antibiotics with this indication, according to positive results from 2 phase 3 trials.
The positive results were from the EAGLE-2 (NCT04020341) and EAGLE-3 (NCT04187144) phase 3 trials, which were stopped early for efficacy following recommendations made by the Independent Data Monitoring Committee in November 2022.
“Despite uncomplicated [UTIs] being one of the most common infections in women and mounting concern over rising resistance rates to existing treatments, there has been no new class of antibiotics for over 20 years,” Chris Corsico, senior vice president of development at GSK, said in a statement. “We believe that gepotidacin, if approved, will offer a much-needed additional oral treatment option for patients at risk of treatment failure associated with resistance or recurrence of uUTI.”
“We are committed to working with global regulators to bring this new antibiotic to patients as quickly as possible,” he said.
In both studies, gepotidacin demonstrated non-inferiority to nitrofurantoin, an existing first-line treatment for uUTI, in individuals with confirmed UTI and a uropathogen susceptible to nitrofurantoin.
Specifically in the EAGLE-3 trial, gepotidacin demonstrated statistically significant superiority compared with nitrofurantoin.
The results are based on the primary efficacy endpoint of therapeutic success, an endpoint comprising clinical resolution and microbiological eradication of bacteria at the test-of-cure visit 10 to 13 days after the initiation of treatment.
In the EAGLE-2 trial, gepotidacin demonstrated therapeutic success in 50.6% of individuals compared with 47% for those receiving nitrofurantoin. For the EAGLE-3 trial, the therapeutic success was 58.5% and 43.6%, respectively.
For both trials, approximately 94% of individuals treated with gepotidacin did not receive an additional antibiotic for uUTI during the participation of the trial and through the follow-up visit on day 28.
The safety and tolerability profile for the drug in both trials was consistent with previous trials of the drug.
Additionally, gepotidacin demonstrated consistent efficacy compared with nitrofurantoin in key subgroups, including individuals with Escherichia coli pathogens resistant to other antibiotics, patients with a history of recurrence, and those aged older than 50 years.
The subgroups have a high risk of treatment failure.
The clinical success was 65.6% for gepotidacin and 65.2% for nitrofurantoin for EAGLE-2. For EAGLE-3, the clinical success was 67.9% and 63.3%, respectively. The microbiological success of gepotidacin was 72.5% and 72.2%, for the EAGLE-2 and EAGLE-3, respectively, and 67.6% and 57.2%, respectively, for nitrofurantoin.
The EAGLE-3 trial also met the pre-defined boundary for superiority.
The most reported adverse events (AEs) in gepotidacin was gastrointestinal, with diarrhea the most common, followed by nausea. Most of the AEs were mild and moderate in severity.
The data were presented as an oral presentation at the European Congress of Clinical Microbiology and Infectious Diseases in Copenhagen, Denmark. The full results will be submitted for publication in a peer-reviewed scientific journal this year.
Gepotidacin’s positive phase III data shows potential to be the first in a new class of oral antibiotics for uncomplicated urinary tract infections in over 20 years. News release. GSK. April 15, 2023. Accessed April 18, 2023. https://www.gsk.com/en-gb/media/press-releases/gepotidacin-s-positive-phase-iii-data-shows-potential-to-be-the-first-in-a-new-class-of-oral-antibiotics-for-uncomplicated-urinary-tract-infections/