Subgroup Analysis of Pooled Phase 3 Efficacy Data From Two Randomized Trials of Gepotidacin Versus Nitrofurantoin in Uncomplicated Urinary Tract Infections (EAGLE-2 and EAGLE-3) Including Participants With Uropathogens Not-Susceptible to Nitrofurantoin
Abstract
Background: Two phase 3 trials (EAGLE-2 [NCT04020341]/EAGLE-3 [NCT04187144]) demonstrated the efficacy of gepotidacin, a novel, first-in-class triazaacenaphthylene antibacterial, versus nitrofurantoin for the treatment of uncomplicated urinary tract infections (uUTIs). Using pooled data, we assessed gepotidacin efficacy across clinically important subgroups, including participants with nitrofurantoin not-susceptible (NTF-NS; ie, resistant, intermediate or no interpretation) uropathogens.
Methods: Female participants aged ≥12 years with uUTI received gepotidacin (1500 mg) or nitrofurantoin (100 mg), both twice daily for 5 days. Therapeutic success at test-of-cure (day 10–13) was defined as combined complete symptom resolution (clinical success) and reduction of baseline qualifying uropathogens from ≥105 to <103 CFU/mL (microbiological success), without other systemic antibacterials. Response rates at test-of-cure were descriptively summarized in the pooled microbiological intent-to-treat (micro-ITT) nitrofurantoin-susceptible (NTF-S) and NTF-NS populations, and across prespecified subgroups.
Results: In the micro-ITT NTF-S population, treatment differences (in favor of gepotidacin) [95% confidence interval] for therapeutic, clinical and microbiological success were: 9.6% [4.1, 15.2], 2.8% [−2.4, 8.1], and 10.4% [5.2, 15.6]. Corresponding treatment differences were higher in the micro-ITT NTF-NS population: 20.8% [9.2, 32.4], 10.3% [−1.4, 22.1], 20.7% [9.2, 32.3]. In both of these populations, gepotidacin success rates (all endpoints) were similar to or higher than nitrofurantoin across prespecified subgroups at higher risk for antimicrobial resistant uropathogens (age >50 years, history of recurrent uUTI, diabetes, mild renal impairment, extended-spectrum β-lactamase-producing or fluoroquinolone-resistant uropathogens).
Conclusions: Gepotidacin demonstrated efficacy with generally higher therapeutic success rates versus nitrofurantoin in participants with NTF-S and NTF-NS uropathogens, and across a range of key subgroups.
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BibTeX
@article{sheets2026subgroup,
title = {{Subgroup Analysis of Pooled Phase 3 Efficacy Data From Two Randomized Trials of Gepotidacin Versus Nitrofurantoin in Uncomplicated Urinary Tract Infections (EAGLE-2 and EAGLE-3) Including Participants With Uropathogens Not-Susceptible to Nitrofurantoin}},
author = {Amanda Sheets and Jeremy Dennison and Jennifer H Han and Sarah Watts and Caroline Perry and Nicole E Scangarella-Oman and Deborah Butler and John Breton and Thomas M Hooton and Helen Millns and Matthew Helgeson and Salim Janmohamed},
journal = {Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America},
year = {2026},
month = jul,
doi = {10.1093/cid/ciag408},
url = {https://doi.org/10.1093/cid/ciag408},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Subgroup Analysis of Pooled Phase 3 Efficacy Data From Two Randomized Trials of Gepotidacin Versus Nitrofurantoin in Uncomplicated Urinary Tract Infections (EAGLE-2 and EAGLE-3) Including Participants With Uropathogens Not-Susceptible to Nitrofurantoin
AU - Amanda Sheets
AU - Jeremy Dennison
AU - Jennifer H Han
AU - Sarah Watts
AU - Caroline Perry
AU - Nicole E Scangarella-Oman
AU - Deborah Butler
AU - John Breton
AU - Thomas M Hooton
AU - Helen Millns
AU - Matthew Helgeson
AU - Salim Janmohamed
PY - 2026
DA - 2026/07/08
JO - Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
DO - 10.1093/cid/ciag408
UR - https://doi.org/10.1093/cid/ciag408
AB - Background: Two phase 3 trials (EAGLE-2 [NCT04020341]/EAGLE-3 [NCT04187144]) demonstrated the efficacy of gepotidacin, a novel, first-in-class triazaacenaphthylene antibacterial, versus nitrofurantoin for the treatment of uncomplicated urinary tract infections (uUTIs). Using pooled data, we assessed gepotidacin efficacy across clinically important subgroups, including participants with nitrofurantoin not-susceptible (NTF-NS; ie, resistant, intermediate or no interpretation) uropathogens. Methods: Female participants aged ≥12 years with uUTI received gepotidacin (1500 mg) or nitrofurantoin (100 mg), both twice daily for 5 days. Therapeutic success at test-of-cure (day 10–13) was defined as combined complete symptom resolution (clinical success) and reduction of baseline qualifying uropathogens from ≥105 to <103 CFU/mL (microbiological success), without other systemic antibacterials. Response rates at test-of-cure were descriptively summarized in the pooled microbiological intent-to-treat (micro-ITT) nitrofurantoin-susceptible (NTF-S) and NTF-NS populations, and across prespecified subgroups. Results: In the micro-ITT NTF-S population, treatment differences (in favor of gepotidacin) [95% confidence interval] for therapeutic, clinical and microbiological success were: 9.6% [4.1, 15.2], 2.8% [−2.4, 8.1], and 10.4% [5.2, 15.6]. Corresponding treatment differences were higher in the micro-ITT NTF-NS population: 20.8% [9.2, 32.4], 10.3% [−1.4, 22.1], 20.7% [9.2, 32.3]. In both of these populations, gepotidacin success rates (all endpoints) were similar to or higher than nitrofurantoin across prespecified subgroups at higher risk for antimicrobial resistant uropathogens (age >50 years, history of recurrent uUTI, diabetes, mild renal impairment, extended-spectrum β-lactamase-producing or fluoroquinolone-resistant uropathogens). Conclusions: Gepotidacin demonstrated efficacy with generally higher therapeutic success rates versus nitrofurantoin in participants with NTF-S and NTF-NS uropathogens, and across a range of key subgroups.
SN - 1058-4838
SN - 1537-6591
ER -