GSK's New Drug Gepotidacin Could Be the First Antibiotic for Urinary Tract Infections in 20 Years

On October 16, 2024, global pharmaceutical company GSK announced that the US Food and Drug Administration (FDA) has officially accepted their New Drug marketing application (NDA) for Gepotidacin and granted the drug priority review. This decision signals the promise of Gepotidacin as a new oral antibiotic for the treatment of simple urinary tract infections (uUTI). The drug is indicated for female adult patients weighing not less than 40 kg and for adolescent patients weighing not less than 40 kg and aged 12 years and older. According to the FDA's review schedule, the drug is expected to have a premarket review date (PDUFA) of March 26, 2025.

Gepotidacin is a new class of antibiotics that belongs to first in class, meaning it is the first drug in this class to be developed. Its mechanism of action is unique and different from existing quinolone antibiotics. The chemical structure of Gepotidacin belongs to the class of triazacenaphthenes, which effectively blocks the replication process of bacterial DNA by selectively and evenly inhibiting the bacterial DNA cyclotase (a type of Top II) and Top IV. This dual inhibition makes it possible for Gepotidacin to significantly affect its susceptibility to drugs only when the Top II and Top IV enzymes of bacteria mutate at the same time, thereby reducing the risk of bacterial resistance.

The successful acceptance of the new drug application was supported by positive data from two pivotal Phase III clinical studies, EAGLE-2 and EAGLE-3. Both studies were global, randomized, double-blind, non-inferior Phase III clinical trials involving a total of 3,136 patients. The primary objective of the study was to evaluate the efficacy and safety of Gepotidacin (1500mg twice daily) versus furantoin (100mg twice daily) in the treatment of uUTI. The primary endpoint of the study was the number of patients who had a therapeutic response (both clinical and microbiological) at day 10 to 13 post-treatment, the Test of Cure (TOC) visit.

In the EAGLE-2 study, 50.6 percent of patients treated with Gepotidacin achieved "treatment success," compared to 47.0 percent of patients treated with furantoin. In the EAGLE-3 study, the "treatment success" rate was 58.5 percent in the Gepotidacin group and 43.6 percent in the furantoin group. In addition, in key subgroups at higher risk of treatment failure, including patients infected with other antibiotic-resistant E. coli pathogens, patients with a history of relapse, and patients over 50 years of age, Gepotidacin also demonstrated a non-inferior efficacy comparable to that of furanotoin.

In terms of safety, the most commonly reported adverse events (aes) in the Gepotidacin group were gastrointestinal reactions, with diarrhea (16%) and nausea (9%) being more common. However, most of these adverse events were mild (grade 1, 69%) and moderate (grade 2, 28%), with less severity.

Uncomplicated urinary tract infections (uUTI) are a very common outpatient infection, with more than half of women statistically suffering from a uUTI during their lifetime, and more than a quarter suffering from recurrent uUTI. If Gepotidacin can be successfully marketed, it will be the first new oral antibiotic to treat uUTI in more than 20 years, which will provide patients with a new treatment option that is expected to improve treatment outcomes and reduce resistance issues.