GSK plc announced positive results from the pivotal EAGLE-1 phase III trial for gepotidacin, a potential first-in-class oral antibiotic with a novel mechanism of action for uncomplicated urogenital gonorrhoea (GC) in adolescents and adults. These results will be presented on 30 April 2024 at the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Global in Barcelona, Spain. The results from EAGLE-1 are based on a primary endpoint of microbiological response (success or failure of eliminating the bacterial cause of gonorrhoea) at the Test-of-Cure (ToC) visit 3-7 days after treatment.

The trial showed that gepotidacin (oral, two doses of 3,000mg) was non-inferior with 92.6% success rates when compared to 91.2% success rates for intramuscular (IM) ceftriaxone (500mg) plus oral azithromycin (1,000mg) combinedtherapy, a leading combination treatment regimen for gonorrhoea. The safety and tolerability profile of gepotidacin in the EAGLE-1 trial was consistent with results seen in phase I and II trials. The most commonly reported adverse events (AEs) in gepotidacin subjects were gastrointestinal (GI).

All AEs were mild or moderate (Grade 1 or 2) except for one severe (Grade 3), unrelated event in each treatment arm and one unrelated serious event in the gepotidacin arm. There are an estimated 82 million new cases of gonorrhoea globally each year. In the United States, rates of reported gonorrhoea have increased 118% from 2009 to 2021, with 648,056 cases being reported to the US Centers for Disease Control and Prevention (CDC) in 2022.

The CDC also reported that approximately half of gonorrhoea cases each year in the US are resistant to one antibiotic. GSK is also developing gepotidacin for the potential treatment of uncomplicated urinary tract infections (uUTI). Positive phase III data from the EAGLE-2 and EAGLE-3 trials were presented at the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) in April 2023, and published in the Lancet.

If approved, gepotidacin could be the first in a new class of oral antibiotics in uUTI in over 20 years. EAGLE-1 is the third positive pivotal trial for gepotidacin. The development of gepotidacin has been funded in whole or in part with federal funds from the US Department of Health and Human Services, Administration for Strategic Preparedness and Response, Biomedical Advanced Research and Development Authority (BARDA), under Other Transaction Agreement number HHSO100201300011C and with federal funds awarded by the Defense Threat Reduction Agency under agreement number HDTRA1-07-9-0002.