The company says it plans to begin talking with regulators next year after seeing positive efficacy data in the trials.
A new treatment for uncomplicated urinary tract infection (uUTI) may be on its way sooner than expected after the therapy’s developer announced it had stopped enrollment in its pivotal phase 3 trials due to strong efficacy data.
Drugmaker GSK announced the decision earlier this month. The move affects the EAGLE-2 and EAGLE-3 trials, which were designed to evaluate gepotidacin as a treatment for uUTI in women and adolescents. Gepotidacin is a novel antibiotic that would be the first new class of oral antibiotics for UTI in more than 2 decades if approved, the company said.
GSK said their decision follows a recommendation by the Independent Data Monitoring Committee (IDMC), based on a prespecified interim analysis of safety and efficacy data in more than 3000 patients already enrolled in the trials.
“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,” said Chris Corsico, MD, MPH, GSK’s senior vice president of development, in a statement.
The drug is potentially important not only because it represents an advance in a treatment area that has long been stagnant, but also because of increasing resistance to existing therapies. The company said about 12% of women are diagnosed with a uUTI each year, though the number is higher in women over the age of 65. As many as 44% of infections are believed to be recurrent infections, creating a frustrating problem for many patients. One issue is that the Escherichia coli (E coli) bacteria–a main cause of uUTI—appears to be increasingly resistant to existing antibiotics, creating an urgent need for new therapies. Gepotidacin works by inhibiting bacteria DNA replication by a distinct mechanism of action, and is believed to be effective against most strains of E coli.
Both EAGLE trials were designed to compare gepotidacin (1500 mg, twice daily for 5 days) to the established antibiotic therapy, nitrofurantoin (100 mg, twice daily for 5 days) over a period of 4 weeks. The primary endpoint of both trials is the combined clinical and microbiological response in patients at the test-of-cure visit.
With recruitment for both trials now closed, GSK said it anticipates being able to complete study visits and data collection in the first quarter of 2023, and to publish results from the trials sometime that year. In the meantime, the company said it expects to begin working with regulatory agencies in the first half of the year in hopes of gaining approvals for gepotidacin.
“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,” Corsico said.
The new therapy is part of a public-private partnership between GSK and the United States Biomedical Advanced Research and Development Authority (BARDA), which is part of the government’s Administration for Strategic Preparedness and Response. The partnership, which dates back to 2013, was designed to help fight antibiotic resistance and bioterrorism.