US FDA Grants Priority Review to Gepotidacin for Treating Uncomplicated UTIs in Females

On 16 October 2024, GSK plc announced that the US Food and Drug Administration (FDA) has accepted the New Drug Application (NDA) for gepotidacin, an innovative oral antibiotic aimed at treating uncomplicated urinary tract infections (uUTIs) in female adults and adolescents. Gepotidacin represents a potential breakthrough as the first new class of oral antibiotic for uUTIs in over two decades. The FDA has granted this application Priority Review and set a Prescription Drug User Fee Act (PDUFA) action date of 26 March 2025.

Urinary tract infections (UTIs) are a common affliction, with more than half of all women experiencing them at some point in their lives. Approximately 30% of these women suffer from recurrent UTIs, leading to significant discomfort and limitations in daily activities. The rise of drug-resistant bacteria has made the need for new treatments more urgent, as these infections are becoming increasingly difficult to treat with existing antibiotics.

The NDA for gepotidacin is bolstered by positive results from the pivotal phase III EAGLE-2 and EAGLE-3 trials. These studies demonstrated that gepotidacin was non-inferior to nitrofurantoin, the current standard of care, in treating female adults and adolescents with uUTIs caused by bacteria susceptible to nitrofurantoin. Specifically, the EAGLE-3 trial showed that gepotidacin had a statistically significant higher therapeutic success rate of 58.5% compared to 43.6% for nitrofurantoin. In the EAGLE-2 trial, gepotidacin had a therapeutic success rate of 50.6% versus 47.0% for nitrofurantoin.

The safety and tolerability profile of gepotidacin in these trials was consistent with previous studies. The most commonly reported adverse events were gastrointestinal issues, with diarrhea being the most frequent, followed by nausea. Most gastrointestinal adverse events were mild to moderate in severity, with severe events being rare.

The development of gepotidacin has been partly funded by the US Department of Health and Human Services, specifically the Administration for Strategic Preparedness and Response, Biomedical Advanced Research and Development Authority (BARDA), and the Defense Threat Reduction Agency.

Gepotidacin, discovered by GSK scientists, is a first-in-class triazaacenaphthylene antibiotic that works by inhibiting bacterial DNA replication through a unique mechanism. This novel mode of action allows it to target and inhibit two different Type II topoisomerase enzymes, which are crucial for bacterial DNA replication. Gepotidacin has shown efficacy against various pathogens, including E. coli, S. saprophyticus, and N. gonorrhoeae, even those resistant to current antibiotics.

GSK has been a leader in combating infectious diseases for over 70 years, with a vast and diverse pipeline of medicines and vaccines. The company's expertise spans innovation, access, and stewardship in the fight against antimicrobial resistance. Alongside gepotidacin, GSK has entered into exclusive agreements to expand its antimicrobial portfolio, including a partnership with Spero Therapeutics for the antibiotic tebipenem HBr and an agreement with Scynexis for Brexafemme, an antifungal treatment.

GSK’s commitment to addressing global health challenges is reflected in its ongoing efforts to develop new treatments and preventive measures for diseases with high unmet needs. Through its innovative approaches, GSK aims to enhance the quality of life and healthcare outcomes for patients worldwide.