EAGLE-2 and EAGLE-3 phase III trials for gepotidacin stopped early for efficacy following pre-planned interim analysis by Independent Data Monitoring Committee

This decision was based on a pre-specified interim analysis of efficacy and safety data in over 3000 patients across the trials.

Chris Corsico, SVP, Development, GSK, said: “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. There has been no new class of oral antibiotics for uUTI for over 20 years. With the number of uUTIs caused by resistance bacteria increasing, new antibiotic treatments are necessary. 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.”

The EAGLE-2 and EAGLE-3 trials met the primary efficacy endpoint of combined clinical and microbiological resolution following treatment at the Test-Of-Cure (TOC) visit for gepotidacin versus nitrofurantoin in patients with a confirmed uUTI and a uropathogen sensitive to nitrofurantoin. The IDMC review did not identify any safety concerns. The EAGLE-2 and 3 trials are now closed for recruitment, with final study visits and data collection anticipated during the first quarter of 2023. GSK will work with regulatory authorities to commence regulatory filings for gepotidacin in H1 2023. The full results will also be submitted for presentation at a scientific congress and for publication in a peer-reviewed jurnal in 2023.

The development of gepotidacin is the result of a public-private partnership between GSK, the US government’s Biomedical Advanced Research and Development Authority (BARDA), part of the Administration for Strategic Preparedness and Response at the U.S. Department of Health and Human Services, and Defense Threat Reduction Agency (DTRA) within the Department of Defense. The collaboration with BARDA was established in 2013 with the aim to support the development of antibiotics to fight antibiotic resistance and bioterrorism under contract number HHSO100201300011C.

uUTIs are one of the most common infections in the community. The annual incidence of uUTI (or acute cystitis) in women is 12% and c.˜20% in women over 65; 30-44% of uUTI episodes are recurrent. Escherichia coli (e. coli) bacteria are the main cause of uUTI1 but it is showing increasing resistance to antibiotics currently used leaving healthcare professionals with fewer oral options to treat their patients. As a result, there is a need to develop new oral antibiotics that may help treat uUTIs and potentially combat antimicrobial resistance (AMR) in the community, particularly given that there has not been a new class of oral antibiotics for uUTI for over 20 years.

About the EAGLE (Efficacy of Antibacterial Gepotidacin Evaluated) phase III programme. The phase III clinical programme for gepotidacin in adults and adolescents comprises three trials: EAGLE-2 (non-inferiority uUTI trial, 204989) compares the efficacy and safety of gepotidacin (1500mg administered orally twice daily for 5 days) to nitrofurantoin (100mg administered orally twice daily for five days). The trial duration for participants is approximately 28 days. The primary endpoint is the combined clinical and microbiological response at the TOC visit in patients with qualifying uropathogens. EAGLE-3 (non-inferiority uUTI trial, 212390) compares the efficacy and safety of gepotidacin (1500mg administered orally twice daily for 5 days) to nitrofurantoin (100mg administered orally twice daily for 5 days). The trial duration for participants is approximately 28 days up until follow-up. The primary endpoint is the combined clinical and microbiological response at the TOC visit in patients with qualifying uropathogens. EAGLE-1 (non-inferiority urogenital gonorrhoea trial, BTZ116577) compares the efficacy and safety of gepotidacin (3000mg administered orally at the trial site during the baseline visit followed by self-administration of a second oral 3000mg dose as an outpatient 10 to 12 hours after the first dose) to a single intramuscular 500mg dose of ceftriaxone plus a single oral 1g dose of azithromycin in approximately 600 patients with uncomplicated GC caused by the bacterium NG. The trial duration is approximately 21 days. At the TOC visit, the primary endpoint is the culture-confirmed bacterial eradication of NG from the urogenital body site. The EAGLE-1 trial is investigating gepotidacin for the treatment of uncomplicated urogenital gonorrhoea and is ongoing.

EAGLE-2 and 3 are similar trials and together provide substantial clinical evidence, with EAGLE-2 providing additional pharmacokinetic data and EAGLE-3 including an on-treatment ECG test. Trial enrolment overlapped with the COVID-19 pandemic (the EAGLE-2 trial started in October 2019, and the EAGLE-3 trial began in May 2020), and trial sites are located across 12 countries, each with different infection and resistance patterns.