FDA approves gepotidacin for uncomplicated UTI treatment

FDA approves gepotidacin for uncomplicated UTI treatment | Image Credit: © Tada Images - © Tada Images - stock.adobe.com.

The FDA has approved gepotidacin (Blujepa; GSK), for use in treating uncomplicated urinary tract infections (uUTIs) in female patients aged at least 12 years and weighing at least 40 kg, according to GSK.¹

Ryan Haumschild, PharmD, MS, MBA, CPEL, vice president of pharmacy at Emory Healthcare and Winship Cancer Institute, highlighted the importance of the approval. "I think the value [of gepotidacin] for uncomplicated UTIs is still really high. Because we have therapies that we can utilize, such as nitrofurantoin or fluoroquinolones, but at the same time, we've utilized those for a little while, and so individuals' antibiograms might show some type of resistance," he said.

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Impact of uUTIs and the need for treatment

Throughout their lifetime, over 50% of women experience uUTIs, with recurrent infection reported in approximately 30%.¹ This can lead to discomfort and restriction of daily activities, posing a significant patient burden.

“New treatments are needed as the number of uUTIs caused by drug-resistant bacteria is increasing and can result in higher treatment failure rates,” wrote GSK. “Gepotidacin is a late-stage antibiotic in GSK’s growing infectious disease portfolio and could be the first in a new class of oral antibiotics for uUTIs in over 20 years.”¹

As a first-in-class triazaacenaphthylene antibiotic, gepotidacin uses a distinct bonding site to prevent replication of bacterial DNA. In most pathogens, this inhibits 2 different type 2 topoisomerase enzymes, allowing for activity against the target uropathogens and N. gonorrhoeae. This includes those able to resist current antibiotics.¹

Safety and efficacy of gepotidacin

The efficacy and safety of gepotidacin was proven in the EAGLE-2 and EAGLE-3 phase 3 trials, comparing the drug administered as 1500 mg orally twice per day for 5 days with nitrofurantoin 100 mg administered orally for the same duration. Participants included 1531 female adults and 1605 adolescents with uUTIs.¹

Follow-up lasted for approximately 28 years, with the combined clinical and microbiological response at the Test-of-Cure visit at day 10 to 13 reported as the primary outcome. This followed the EAGLE-1 trial, which compared the safety and efficacy of gepotidacin to ceftriaxone plus azithromycin in patients with uncomplicated urogenital gonorrhea.¹

Superiority was reported for gepotidacin compared to nitrofurantoin in EAGLE-3, with therapeutic success occurring in 58.5% and 43.6% of patients receiving these treatments, respectively. This indicated a treatment difference of 14.6%.¹

In the EAGLE-2 trial, similar results were reported, with therapeutic success rates of 50.6% of the gepotidacin group and 47% of the nitrofurantoin group. This indicated a treatment difference of 4.3%.¹

Gepotidacin also displayed safety and tolerability profiles consistent with prior trials. Gastrointestinal (GI) adverse events (AEs) were the most common type reported in patients taking gepotidacin, with diarrhea occurring in 16% and nausea in 9%.¹

Of GI AEs reported among patients taking gepotidacin, 69% were mild at Grade 1 and 28% were moderate at Grade 2. Three percent of patients with GI events had Grade 3 events, vs under 1% of all participants. Both the gepotidacin and nitrofurantoin treatment arms reported a single drug-related serious adverse event across both trials.¹

“[Gepotidacin] target-specific mutations in both enzymes are needed to significantly affect susceptibility to [gepotidacin]." wrote GSK.² "Therefore, a lower potential for resistance development is expected.

According to GSK, gepotidacin will launch in the second half of 2025.²

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 March 19, 2025. 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. Blujepa (gepotidacin) approved by US FDA for treatment of uncomplicated urinary tract infections (uUTIs) in female adults and paediatric patients 12 years of age and older. GSK. March 25, 2025. Accessed March 25, 2025. https://www.gsk.com/en-gb/media/press-releases/blujepa-gepotidacin-approved-by-us-fda-for-treatment-of-uncomplicated-urinary-tract-infections/