GSK Gepotidacin accepted for priority review by USFDA for oral treatment of uncomplicated urogenital gonorrhoea

The US application is based on results from the EAGLE-1 phase III trial recently published in The Lancet, showing that gepotidacin (oral, two doses of 3,000mg) was non-inferior, with 92.6% (187/202, [95% CI 88·0 to 95·8]) success rates at urogenital site when compared to 91.2% (186/204, [95% CI 86.4-94.7]) success rates for intramuscular ceftriaxone (500mg) plus oral azithromycin (1,000mg) combined therapy, a leading combination treatment regimen for gonorrhoea. Additionally, there were no failures at the urogenital site due to bacterial persistence of N. gonorrhoeae in either treatment arm. The safety and tolerability profile of gepotidacin in the EAGLE-1 trial was consistent with results seen in previous clinical trials, with no serious drug related adverse events observed in either the gepotidacin or the comparator arm. The most common reported adverse reactions were mild to moderate gastrointestinal events.

This is the second major indication filed in the US for gepotidacin, and review of regulatory submissions for the uUTI indication is also ongoing in the UK and Australia.

The development of gepotidacin has been funded 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 US Department of Defense’s Threat Reduction Agency under agreement number HDTRA1-07-9-0002.

Gepotidacin, discovered by GSK scientists, is a bactericidal, first-in-class triazaacenaphthylene antibiotic that inhibits bacterial DNA replication by a distinct binding site, a novel mechanism of action, and for most pathogens, provides well-balanced inhibition of two different Type II topoisomerase enzymes. This provides activity against Neisseria gonorrhoeae and most target uropathogens (such as Escherichia coli and Staphylococcus saprophyticus), including isolates resistant to current antibiotics. Due to this well-balanced inhibition for most pathogens, a single target-specific mutation may not significantly impact gepotidacin activity.