Objective:

To report the FDA approval of gepotidacin for treating uncomplicated urinary tract infections (uUTIs).

Approach:

• Study Design: Two randomized, double-blind, active-controlled phase III trials (EAGLE-2 and EAGLE-3) were conducted to evaluate gepotidacin.
• Participants: EAGLE-2 enrolled 1,531 participants and EAGLE-3 enrolled 1,605 participants, all female patients with culture-confirmed uUTIs.
• Treatment Comparison: Gepotidacin (1,500 mg orally twice daily for 5 days) was compared with nitrofurantoin (100 mg orally twice daily for 5 days).
• Primary Endpoint: Therapeutic success was defined as a composite of clinical resolution and microbiological eradication, assessed at the test-of-cure visit (days 10–13).

Key Findings:

• In EAGLE-2, gepotidacin achieved therapeutic success in 50.6% (162 of 320) of patients versus 47.0% (135 of 287) for nitrofurantoin.
• In EAGLE-3, gepotidacin demonstrated superiority with therapeutic success in 58.5% (162 of 277) compared to 43.6% (115 of 264) for nitrofurantoin.
• The safety profile of gepotidacin was consistent with prior studies, with gastrointestinal adverse events being the most common, including diarrhea (16%) and nausea (9%).

Interpretation:

Gepotidacin is the first oral antibiotic with a new mechanism of action approved for uUTIs in nearly 30 years.

Limitations:

• The trials were limited to female patients aged 12 years or older and weighing at least 88.2 pounds.
• The long-term safety and efficacy of gepotidacin beyond the study period are not yet established.

Conclusion:

A U.S. commercial launch of gepotidacin is anticipated in the second half of 2025.

Sources:

• GSK Press Release