GSK Announces Positive Phase III Results for Novel Antibiotic Gepotidacin in Uncomplicated UTI, Plans NDA Submission in Q2 2023

On April 15, GSK announced positive data from two pivotal Phase III studies (EAGLE-2 and EAGLE-3) of the next-generation antibiotic Gepotidacin for the treatment of uncomplicated urinary tract infections (uUTI) at the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID). In both studies,，Gepotidacin is non-inferior to Nitrofurantoin. Based on the study results, GSK will submit the marketing application for Gepotidacin to the FDA in Q2 2023.

Gepotidacin is a first-in-class novel oral antibiotic developed by GSK that targets topoisomerase II (Top II). Its structure belongs to the triazaacene class, which is different from existing quinolone antibiotics. Compared with quinolone antibiotics (which solely inhibit Top II or Top IV), Gepotidacin has a completely new mechanism of action, selectively and evenly inhibiting bacterial DNA gyrase (a type of Top II) and Top IV, thereby suppressing bacterial DNA replication. Since Gepotidacin exerts balanced inhibition on both Top II and Top IV, significant resistance to Gepotidacin will only occur when mutations happen in both enzymes.

Gepotidacin Structure

EAGLE-2 and EAGLE-3 are both global, randomized, double-blind, non-inferiority (margin of 10%) clinical trials, enrolling a total of 3,136 patients to evaluate the efficacy and safety of Gepotidacin (1500mg, twice daily) compared with nitrofurantoin (100mg, twice daily) in the treatment of uUTI. The primary endpoint is the number of patients achieving a treatment response (including clinical response and microbiological response) during the test-of-cure (TOC) visit on days 10–13.

In the EAGLE-2 study, 50.6% of patients in the Gepotidacin group achieved "treatment success," compared to 47.0% in the nitrofurantoin group. In the EAGLE-3 study, 58.5% of patients in the Gepotidacin group achieved "treatment success," compared to 43.6% in the nitrofurantoin group. Additionally, in key subgroups with a higher risk of treatment failure, Gepotidacin consistently demonstrated non-inferior efficacy to nitrofurantoin, including in patients with *E. coli* pathogens resistant to other antibiotics, patients with a history of recurrence, and patients over 50 years old.

Main Results of EAGLE-2 and EAGLE-3 Studies

(Source: GSK Official Website)

The most commonly reported adverse events (AEs) in the Gepotidacin group were gastrointestinal reactions, with diarrhea (16%) and nausea (9%) being more common. However, the majority of these AEs were mild (Grade 1, 69%) and moderate (Grade 2, 28%) in severity.

Uncomplicated urinary tract infections (uUTI) are the most common outpatient infections, with over half of women experiencing a uUTI in their lifetime and more than a quarter suffering from recurrent uUTI.

Chris Corsico, Senior Vice President (SVP) of Development at GSK, stated: "Despite uUTI being one of the most common infections in women, and the growing concern of antibiotic resistance to existing therapies, there has not been a new antibiotic introduced in over 20 years. We believe that, once approved, Gepotidacin will offer a much-needed additional oral treatment option for patients at risk of treatment failure due to uUTI resistance or recurrence. We are committed to working with global regulatory authorities to bring this novel antibiotic to patients as soon as possible."

Copyright © 2023 PHARMCUBE. All Rights Reserved.

Welcome to forward, share, and reasonably cite. When citing, please clearly indicate the source of the article; if you need to reprint, please leave a message or send a notification to the WeChat Official Account backend, and include the name and ID of the official account.

Disclaimer: The information in this WeChat article is for general reference only and should not be directly used as decision-making content. PharmaCube assumes no responsibility for any loss incurred by any party due to the use of the content herein.

Wonderful Live Broadcast

CUBE LIVE

PharmaCube Reader Survey Questionnaire

Thank you for your companionship. We look forward to your feedback.

Scan the QR code to provide valuable suggestions