Positive results from the phase 3 EAGLE-1 trial indicate that gepotidacin demonstrated non-inferiority to ceftriaxone plus azithromycin in the treatment of adolescent and adult patients with urogenital gonorrhea. The trial met its primary efficacy end point and results are based off a microbiological response at the test-of-cure visit that occurred 3 to 7 days after treatment.1
Gepotidacin is an investigational bactericidal, first-in-class triazaacenaphthylene antibiotic that inhibits bacterial DNA replication by a novel mechanism of action and binding site. For most pathogens, gepotidacin provides inhibition of 2 different type 2 topoisomerase enzymes and provides activity against most target uropathogens strains, including E. coli and S. saprophyticus. The Efficacy of Antibacterial Gepotidacin Evaluated (EAGLE) phase 3 clinical program consists of 3 trials that compared the efficacy and safety of gepotidacin with ceftriaxone plus azithromycin and nitrofurantoin.1,2
EAGLE-1 (NCT04010539) compared 2 oral 3000-mg doses of gepotidacin with 500 mg of intramuscular (IM) ceftriaxone plus 1000 mg of oral azithromycin in 628 patients aged 12 years and older with uncomplicated urogenital gonorrhea. Patients were randomly assigned to either the experimental group or the active comparator group. In the experimental group, patients received 4 oral 750-mg tablets of gepotidacin, and those in the active comparator group received 500 mg of IM ceftriaxone and 2 oral 500-mg tablets of azithromycin. According to the investigators, the safety and tolerability profiles of gepotidacin in EAGLE-1 were consistent across the prior phase 1 and 2 trials.2
About the Trials
1. EAGLE-1
- Trial Name: A Phase III, Randomized, Multicenter, Open-Label Study in Adolescent and Adult Participants Comparing the Efficacy and Safety of Gepotidacin to Ceftriaxone Plus Azithromycin in the Treatment of Uncomplicated Urogenital Gonorrhea Caused by Neisseria Gonorrhoeae
- ClinicalTrials.gov ID: NCT04010539
- Sponsor: GlaxoSmithKline
- Completion Date: October 10, 2023.
2. EAGLE-2
- Trial Name: A Study to Evaluate Efficacy and Safety of Gepotidacin in the Treatment of Uncomplicated Urinary Tract Infection (UTI)
- ClinicalTrials.gov ID: NCT04020341
- Sponsor: GlaxoSmithKline
- Completion Date: November 30, 2022.
3. EAGLE-3
- Trial Name: Comparative Study to Evaluate Efficacy and Safety of Gepotidacin to Nitrofurantoin in Treatment of Uncomplicated Urinary Tract Infection (UTI)
- ClinicalTrials.gov ID: NCT04187144
- Sponsor: GlaxoSmithKline
- Completion Date: December 1, 2022.
Further, EAGLE-2 and EAGLE-3 were randomized, multicenter, double-blind non-inferiority phase 3 trials that compared gepotidacin with nitrofurantoin. Patients were randomly assigned to receive either 1500 mg of oral gepotidacin twice daily for 5 days, or 100 mg of oral nitrofurantoin twice daily for 5 days. Enrolled patients were aged 12 years and older; assigned female at birth; were not pregnant; and experienced 2 or more symptoms of dysuria, frequency, urgency, or lower abdominal pain with evidence of urinary nitrite, pyuria, or both.
Results from both trials indicate that gepotidacin is an effective treatment for uncomplicated urinary tract infections, demonstrating favorable safety and tolerability profiles. In the EAGLE-2 and EAGLE-3 trials, 50.6% (162 of 320) and 58.5% (162 of 227) of patients, respectively, who were assigned gepotidacin experienced therapeutic success. In addition, patients assigned nitrofurantoin had also experienced positive results, with 47.0% (135 of 287) and 43.6% (115 of 264) of patients, respectively, showing therapeutic success.
“With rising incidence rates and concern around growing resistance to existing treatments, gonorrhea poses a threat to public health globally,” said Chris Corsico, senior vice president of development, GSK, in a press release. “These positive headline results demonstrate the potential for gepotidacin to provide a novel oral treatment option in the face of rising resistance and for patients who cannot take other treatments due to allergies or intolerance.”1
Reference
- GlaxoSmithKline. GSK announces positive headline results from EAGLE-1 phase III trial for gepotidacin in uncomplicated urogenital gonorrhoea (GC). News release. February 26, 2024. Accessed February 26, 2024. https://www.gsk.com/en-gb/media/press-releases/gsk-announces-positive-headline-results-from-eagle-1-phase-iii-trial-for-gepotidacin-in-uncomplicated-urogenital-gonorrhoea-gc/
- A Study Evaluating Efficacy and Safety of Gepotidacin Compared With Ceftriaxone Plus Azithromycin in the Treatment of Uncomplicated Urogenital Gonorrhea.ClinicalTrials.gov identifier: NCT04010539. Updated December 14, 2023. Accessed February 26, 2024. https://clinicaltrials.gov/study/NCT04010539
- 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. Lancet. 2024;403(10428):741-755. doi:10.1016/S0140-6736(23)02196-7
