Gepotidacin meets endpoints for uUTI studies, eyes potential FDA approval this year

During the ongoing European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) GSK presented its data from the pivotal EAGLE-2 and EAGLE-3 phase 3 trials for its investigational antibiotic, gepotidacin, for uUTI.

The trials showed gepotidacin met primary endpoint of non-inferiority to nitrofurantoin; and EAGLE-3 demonstrated statistical superiority.

“These results are a significant step forward in an area that has seen very little innovation for decades. Gepotidacin is the first antibiotic to meet contemporary regulatory criteria, which set a high threshold for the efficacy of treatments in uncomplicated urinary tract infections,” Florian Martin Erich Wagenlehner, MD, principal Investigator for the EAGLE-2 phase 3 trial, said in a statement. “Gepotidacin has the potential to offer healthcare professionals another oral option to treat this common community infection.”

This is a first-in-class oral antibiotic with a novel mechanism of action for uUTI in female adults and adolescents. And if it is approved, it would be the first antibiotic in a new class to get the FDA nod for this indication in over 20 years.

Results
The EAGLE-2 and EAGLE-3 phase 3 trials were near-identical global, randomized, parallel-group, double-blind, non-inferiority (10% margin) trials comparing the efficacy and safety of oral gepotidacin to nitrofurantoin for the treatment of uUTI. A total of 3136 patients were enrolled across both trials.

EAGLE-2 (non-inferiority uUTI trial) compared the efficacy and safety of gepotidacin (1500mg administered orally twice daily for five days) to nitrofurantoin (100mg administered orally twice daily for five days). The trial duration for participants was approximately 28 days.

The primary endpoint was the combined clinical and microbiological response at the ToC visit (days 10-13) in patients with qualifying uropathogens susceptible to nitrofurantoin. EAGLE-3 (non-inferiority uUTI trial) compared the efficacy and safety of gepotidacin (1500mg administered orally twice daily for five days) to nitrofurantoin (100mg administered orally twice daily for five days). The trial duration for participants was approximately 28 days. The primary endpoint was the combined clinical and microbiological response at the ToC visit (days 10-13) in patients with qualifying uropathogens susceptible to nitrofurantoin.

Gepotidacin’s Specifics
This antibiotic, developed by GSK, is a first-in-class triazaacenaphthylene antibiotic that inhibits bacterial DNA replication by a novel mechanism of action and binding site and provides well-balanced inhibition of two different Type II topoisomerase enzymes. This provides activity against most strains of target uropathogens, such as E coli and Staphylococcus saprophyticus, including isolates resistant to current antibiotics. Furthermore, due to the well-balanced inhibition of two enzymes, mutations in both enzymes are needed to significantly affect susceptibility to gepotidacin.

Next Steps
GSK is planning an FDA submission for gepotidacin in this quarter, and believes this therapy could be a welcome antibiotic addition for this indication. “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,” Chris Corsico, MD, MPH, senior vice president, Development, GSK, said in a statement. “We are committed to working with global regulators to bring this new antibiotic to patients as quickly as possible.”

This article was published by our sister publication Contagion Live.