FDA Approves First New Class of Oral Antibiotics for Uncomplicated UTIs in Nearly 30 Years

The FDA has approved gepotidacin (Blujepa; GSK) to treat uncomplicated urinary tract infections (uUTIs) in female patients aged 12 and older, introducing the first new class of oral antibiotics for this condition in nearly 30 years.¹

More than half of all women experience a uUTI in their lifetime, with about 30% developing recurrent infections, leading to significant patient burden, including discomfort and limitations in daily activities.² Also, the growing number of uUTIs due to drug-resistant bacteria further underscores the need for new treatment options; resistance can contribute to higher rates of treatment failure.

"The approval of Blujepa is a crucial milestone with uUTIs among the most common infections in women," Tony Wood, chief scientific officer of GSK, said in a press release.¹ "We are proud to have developed Blujepa, the first in a new class of oral antibiotics for uUTIs in nearly 3 decades, and to bring another option to patients given recurrent infections and rising rates of resistance to existing treatments."

The US commercial launch is planned for the second half of 2025.

The approval of gepotidacin (Blujepa; GSK) introduces the first new class of oral antibiotics for uncomplicated urinary tract infections (uUTIs) in nearly 30 years. | Image Credit: wladimir1804 - stock.adobe.com

The approval was supported by positive results from the phase 3 EAGLE-2 (NCT04020341) and EAGLE-3 (NCT04187144) trials, which compared the efficacy and safety of oral gepotidacin with that of the antibiotic nitrofurantoin in adolescent and adult female patients with uUTIs.³ EAGLE-2 was conducted from October 17, 2019, to November 30, 2022, and EAGLE-3 took place from April 23, 2020, to December 1, 2022.

In both trials, eligible patients included non-pregnant females aged 12 or older who weighed at least 40 kg. They also had to present with evidence of urinary nitrite, pyuria, or both, along with at least 2 of the following symptoms: dysuria, frequency, urgency, or lower abdominal pain. Patients were enrolled at 1 of 219 centers worldwide and randomly assigned to receive either oral gepotidacin (1500 mg twice daily for 5 days) or oral nitrofurantoin (100 mg twice daily for 5 days).

The primary endpoint was therapeutic response at the test-of-cure visit (day 10-13), which was assessed in patients with nitrofurantoin-susceptible qualifying uropathogens (≥ 10⁵ colony-forming units per mL) and who received at least one treatment dose. Following regulatory guidance, therapeutic success was defined as a combination of clinical and microbiological success without other systemic antimicrobials. Also, safety analyses included all patients who received at least one treatment dose.

In EAGLE-2, therapeutic success was observed in 50.6% (n = 162) of patients treated with gepotidacin and 47.0% (n = 135) of those treated with nitrofurantoin (adjusted difference, 4.3%; 95% CI, –3.6 to 12.1). Similarly, in EAGLE-3, therapeutic success rates were 58.5% (n = 162) for patients treated with gepotidacin and 43.6% (n = 115) for those treated with nitrofurantoin (adjusted difference, 14.6%; 95% CI, 6.4-22.8).

The researchers determined that gepotidacin was non-inferior to nitrofurantoin in both studies, but it demonstrated superiority in EAGLE-3. Regarding gepotidacin’s safety profile, the most common adverse event was diarrhea, occurring in 14% (n = 111) of patients in EAGLE-2 and 18% (n = 147) of patients in EAGLE-3. However, most cases were mild or moderate, with no life-threatening or fatal events reported.

“As a first-in-class investigational oral antibiotic with activity against common uropathogens associated with uUTIs (including those with drug-resistant phenotypes), gepotidacin has the potential to offer substantial benefit to patients,” the authors concluded. “Gepotidacin could become an additional oral treatment option for patients with uUTIs and treating physicians.”

References

1. 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. News release. 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/
2. Gepotidacin accepted for priority review by US FDA for treatment of uncomplicated urinary tract infections in female adults and adolescents. News release. GSK; October 16, 2024. Accessed March 25, 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/
3. Wagenlehner F, Perry CR, Hooton TM, et al. Oral gepotidacin versus nitrofurantoin in patients with uncomplicated urinary tract infection (EAGLE-2 and EAGLE-3): two randomised, controlled, double-blind, double-dummy, phase 3, non-inferiority trials. The Lancet. doi:10.1016/s0140-6736(23)02196-7