The outcomes of two part 3 trials that had been stopped early after interim evaluation confirmed that an investigational antibiotic gepotidacin met its objectives in girls with uncomplicated urinary tract an infection (uUTI) had been revealed yesterday in The Lancet.
The double-blind, non-inferiority EAGLE-2 and EAGLE-3 trials enrolled adolescent and grownup girls with signs of uUTI at 219 facilities worldwide and randomly assigned them to obtain oral gepotidacin or oral nitrofurantoin for five days, with randomization stratified by age class and historical past of recurrent UTIs. The first finish level was therapeutic response (success or failure) at test-of-cure (days 10 to 13), with therapeutic success outlined as mixed scientific success (full symptom decision) and microbiologic success (discount of qualifying uropathogens).
Developed by British drugmaker GSK, gepotidacin is a first-in-class triazaacenaphthylene antibiotic that inhibits bacterial DNA replication by a novel mechanism of motion. GSK introduced that the trials had been stopped early in November 2022.
Efficacy noticed in opposition to resistant uropathogens
The interim evaluation confirmed that gepotidacin was non-inferior in each trials and superior in EAGLE-3. Within the EAGLE-2 trial, 162 (50.6%) of 320 sufferers within the gepotidacin group had therapeutic success, in contrast with 135 (47.0%) of 287 sufferers assigned nitrofurantoin (adjusted distinction, 4.3 proportion factors; 95% confidence interval [CI], –3.6 to 12.1). In EAGLE-3, 162 (58.5%) of 277 sufferers assigned gepotidacin achieved therapeutic success, in contrast with 115 (43.6%) of 264 sufferers within the nitrofurantoin group (adjusted distinction, 14.6 proportion factors; 95% CI, 6.4 to 22.8).
The most typical opposed occasion with gepotidacin was diarrhea, which was noticed in 14% of sufferers in EAGLE-2 and 18% in EAGLE-3.
As well as, a subgroup anaylsis discovered that therapeutic success charges in sufferers with uUTIs brought on by Escherichia coli, together with drug-resistant phenotypes of scientific significance, usually favored gepotidacin.
The investigators say gepotidacin’s favorable security profile and efficacy in opposition to resistant pathogens might present “substantial advantages” to sufferers.
“Due to the rising worldwide prevalence of antimicrobial resistance, these findings recommend that gepotidacin has potential as a brand new oral therapy for uncomplicated urinary tract infections brought on by widespread uropathogens immune to present therapies,” they wrote.