FDA Grants Priority Review to GSK’s Gepotidacin for Uncomplicated Urinary Tract Infections

Image Credit: Adobe Stock Images/220 Selfmade studio

The FDA has granted Priority Review to a New Drug Application (NDA) for GSK’s gepotidacin, a novel oral antibiotic for the treatment of uncomplicated urinary tract infections (uUTIs) in females and adolescents. According to the company, the NDA was supported by positive results from the pivotal Phase III EAGLE-2 and EAGLE-3 trials, which found that gepotidacin demonstrated non-inferiority to nitrofurantoin, the current standard-of-care for uUTIs.

EAGLE-2 and EAGLE-3 compared the efficacy and safety of gepotidacin (1,500 mg administered orally twice daily for five days) to nitrofurantoin (100 mg administered orally twice daily for five days). The trial enrolled 1531 adult females and 1605 adolescents with uUTIs, with a primary endpoint of the combined clinical and microbiological response at the Test-of-Cure (ToC) visit between 10 and 13 days in patients with qualifying uropathogens susceptible to nitrofurantoin.

Gepotidacin demonstrated therapeutic success in 58.5% of participants compared to 43.6% for nitrofurantoin in the EAGLE-3 trial. In EAGLE-2, gepotidacin demonstrated therapeutic success in 50.6% of participants compared to 47% of participants administered nitrofurantoin.

The safety and tolerability profile of gepotidacin in both studies was found to be consistent with previous trials and no new safety signals were reported. Common adverse events (AEs) associated with gepotidacin included gastrointestinal issues such as diarrhea and nausea. Investigators reported that 69% of AEs were mild, 28% were moderate, and only 3% were reported to be severe. Both treatment arms had one drug-related serious AE.¹

Results from the EAGLE-2 and EAGLE-3 trials were first published in April 2023, with an oral presentation at the European Congress of Clinical Microbiology and Infectious Diseases.²

“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. 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. We are committed to working with global regulators to bring this new antibiotic to patients as quickly as possible,” said Chris Corsico, SVP development, GSK, in a press release.

According to Medscape, UTIs are common in women and account for approximately eight million visits to various types of healthcare facilities in the United States per year. On average, around 20% of women are expected to suffer from a UTI in their lifetime. Most UTIs are considered to be cystitis, with other types including pyelonephritis, which refers to upper UTI, and bacteriuria or funguria, which describe findings of bacteria or yeast, respectively, in the urine.³

Medscape also stated that the incidence for UTIs in males increases in those over 50 years of age progressively. As a result of the male urinary tract’s many defenses, infections usually are associated with anatomic abnormalities, which often require surgical correction. These surgeries frequently result from prostatitis involving bladder neck obstruction, prostatic or bladder calculi, or recurrent prostatitis with the same bacteria.⁴

“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 EAGLE-2 trial principal investigator Florian Martin Erich Wagenlehner, in the press release.

References

1. Gepotidacin accepted for priority review by US FDA for treatment of uncomplicated urinary tract infections in female adults and adolescents. GSK. October 16, 2024. Accessed October 18, 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. April 15, 2023. Accessed October 18, 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/#:~:text=In%20the%20EAGLE%2D2%20phase,with%20previous%20trials%20of%20gepotidacin.

3. Urinary Tract Infection (UTI) and Cystitis (Bladder Infection) in Females. Medscape. February 26, 2024. Accessed October 18, 2024. https://emedicine.medscape.com/article/233101-overview#:~:text=UTIs%20in%20women%20are%20very,those%20visits%20are%20to%20EDs.

4. Urinary Tract Infection (UTI) in Males. Medscape. February 26, 2024. Accessed October 18, 2024. https://emedicine.medscape.com/article/231574-overview