Gepotidacin Receives FDA Priority Review for the Treatment of Uncomplicated Urinary Tract Infections

The FDA has accepted a New Drug Application (NDA) for gepotidacin (GSK) for the treatment of female adults and adolescents 12 years of age and older with uncomplicated urinary tract infections (uUTIs). Additionally, the FDA has granted Priority Review for this application, with a Prescription Drug User Fee Act action date in March of 2025. If approved, the investigational drug could be the first-in-class oral antibiotic treatment for uUTIs in over 20 years, according to study authors.¹

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“Despite uncomplicated urinary tract infections being one of the most common infections in women and mounting concern over rising resistance rates to existing treatments, there has been no new class of antibiotics for over 20 years,” said Chris Corsico, senior vice president of development at GSK, in a news release.²

A UTI is a bacterial infection of the bladder that can occur in any individual with a normal urinary tract, despite not having other medical conditions. Symptoms include pain or burning when urinating, frequent urination, sudden urge to urinate, and blood in the urine. uUTIs are cystitis or lower tract UTIs that are more common among young, sexually active women.³ More than half of all women develop uUTIs in their lifetime and around 30% experience recurrent uUTIs, which can cause significant discomfort.¹ uUTIs typically resolve on their own, but individuals can receive antibiotics or take pain killers to soothe symptoms.³

“We believe that gepotidacin, if approved, will offer a much-needed additional oral treatment option for patients at risk of treatment failure associated with resistance or recurrence of uUTI,” Corsico said in the news release.²

The study authors noted that gepotidacin is an investigational bactericidal, first-in-class triazaacenaphthylene antibiotic. Its role is to inhibit bacterial DNA replication by a distinct binding site to provide balanced inhibition of 2 different type II topoisomerase enzymes.¹

The NDA was based on positive findings from the phase 3 EAGLE-2 and EAGLE-3 trials that compared to efficacy and safety of gepotidacin to nitrofurantoin, the current standard of care for uUTIs. A total of 3136 female adults and adolescents with uUTIs were included in both studies that were assigned to receive 1500 mg of gepotidacin orally twice daily for 5 days, compared with 100 mg of nitrofurantoin orally twice daily for 5 days.^1,2

The results found that gepotidacin displayed non-inferiority to nitrofurantoin among female adults and adolescents with a confirmed uUTI and a uropathogen prone to nitrofurantoin. Additionally, in EAGLE-2, gepotidacin showed therapeutic success in 50.6% of individuals, compared to 47.0% for nitrofurantoin. In EAGLE-3, gepotidacin displayed statistically significant superiority, compared to nitrofurantoin with 58.5% versus 43.6%, according to study authors.¹

The study authors noted that the most common adverse events with gepotidacin were diarrhea (16%) and nausea (9%).¹

“These results are a significant step forward in an area that has seen very little innovation for decades. Gepotidacin is the first antibiotic to meet contemporary regulatory criteria, which set a high threshold for the efficacy of treatments in uncomplicated urinary tract infections. Gepotidacin has the potential to offer healthcare professionals another oral option to treat this common community infection,” said Florian Martin Erich Wagenlehner, MD, principal investigator for the EAGLE-2 phase III trial, in a news release.²

REFEREENCES

1. Gepotidacin accepted for priority review by US FDA for treatment of uncomplicated urinary tract infections in female adults and adolescents. GSK. News release. October 16, 2024. Accessed October 16, 2024. https://www.gsk.com/en-gb/media/press-releases/gepotidacin-accepted-for-priority-review-by-us-fda-for-treatment-of-uncomplicated-urinary-tract-infections-in-female-adults-and-adolescents/.

2. Gepotidacin’s positive phase III data shows potential to be the first in a new class of oral antibiotics for uncomplicated urinary tract infections in over 20 years. GSK. News release. April 15, 2023. Accessed October 16, 2024. https://www.gsk.com/en-gb/media/press-releases/gepotidacin-s-positive-phase-iii-data-shows-potential-to-be-the-first-in-a-new-class-of-oral-antibiotics-for-uncomplicated-urinary-tract-infections/.

3. Uncomplicated Urinary Tract Infections. StatPearls. News release. November 13, 2023. Accessed October 16, 2024. https://www.ncbi.nlm.nih.gov/books/NBK470195/#:~:text=An%20uncomplicated%20urinary%20tract%20infection,%5D%5B3%5D%5B4%5D.