With endpoints already met, GSK halts trial into new antibiotic
GSK announced that two Phase III trials evaluating gepotidacin to treat uncomplicated urinary tract infection (uUTI) had been halted early for efficacy. The decision was made following a recommendation by an independent data monitoring committee.
According to the company, the committee had conducted an interim analysis of efficacy and safety data in the 3,000 patients across the trial, which led to their recommendation to stop enrolment into the trials.
The action was taken on two trials, EAGLE-2 and EAGLE-3, that had met their primary efficacy endpoint of combined clinical and microbiological resolution, following treatment at the Test-Of-Cure visit for gepotidacin versus nitrofurantoin in patients with a confirmed uUTI and a uropathogen sensitive to nitrofurantoin.
GSK stated that the review by the committee did not identify any safety concerns for the antibiotic.
The company will begin filing with regulators for gepotidacin in the first half of 2023, with final study visits and data collection expected to take place during the first quarter of 2023. Full results of the trials will be presented during the course of next year.
GSK has been working alongside the US government’s Biomedical Advanced Research and Development Authority (BARDA) to develop the antibiotic. The two organizations have been working together on developing new antibiotics since 2013, with the overall aim to fight antibiotic resistance and bioterrorism.
Gepotidacin itself is a novel, investigational bactericidal, first-in-class triazaacenaphthylene antibiotic. The compound is able to inhibit bacterial DNA replication by binding to two different Type II topoisomerase enzymes.
According to GSK, this delivers activity against most strains of E. coli and S. saprophyticus. In addition, due to the equal and independent binding at both enzymes, mutations in both enzymes are needed to significantly affect gepotidacin susceptibility – making it less likely for resistance to develop.
The success of the trials arrive shortly after GSK broadened its pipeline of antibiotics through a $66m (€68m) acquisition of Spero’s late-stage antibiotic for complicated urinary tract infection.
Chris Corsico, SVP, development, GSK, said: “Uncomplicated urinary tract infections 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.”
The need to develop various options against urinary tract infections is rising because there is increasing resistance to current antibiotics used.