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In a trial that compared gepotidacin to ceftriaxone plus azithromycin in patients with urogenital gonorrhea, gepotidacin presented a 92.6% microbiological success rate.
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Trial Name: A Study Evaluating Efficacy and Safety of Gepotidacin Compared With Ceftriaxone Plus Azithromycin in the Treatment of Uncomplicated Urogenital Gonorrhea
ClinicalTrials.gov ID: NCT04010539
Sponsor: GlaxoKlineSmith
Completion Date: October 10, 2023
Positive results from the EAGLE-1 trial (NCT04010539), a phase 3 trial which evaluated gepotidacin (GlaxoKlineSmith) for the treatment of uncomplicated urogenital gonorrhea (GC) in adolescents and adults, were announced. According to the investigators, the study met its primary endpoint and demonstrated consistent safety and tolerability profiles that were present in the prior phase 1 and 2 trials. The results will be presented at the European Society of Clinical Microbiology and Infectious Diseases Global in Barcelona, Spain, on April 30, 2024.
Gepotidacin is an investigational bactericidal, first-in-class triazaacenaphthylene antibiotic that inhibits the replication of bacterial DNA. The drug’s mechanism of action and binding site for most pathogens provides the inhibition of 2 different type 2 topoisomerase enzymes—such as Escherichia coli and Staphylococcus saprophyticus—as well as Neisseria gonorrhoeae, including isolates that are resistant to multiple antibiotics. Gepotidacin target-specific mutations in both enzymes are necessary to significantly affect the susceptibility of gepotidacin because of the well-balanced inhibition of the 2 enzymes.
The EAGLE-1 trial is 1 of 3 trials included in the EAGLE program—EAGLE-1 evaluates non-inferiority uncomplicated GC, and EAGLE-2 and EAGLE-3 evaluate non-inferiority uncomplicated urinary tract infections (uUTIs)—that tested the efficacy and safety of oral gepotidacin (2 doses of 3000 mg) in patients. The treatment was compared with intramuscular ceftriaxone (500 mg) plus oral azithromycin (1000mg) in approximately 600 patients with uncomplicated GC.
The results indicated that gepotidacin was non-inferior to ceftriaxone plus azithromycin, showing a 92.6% success rate compared with 91.2%, respectively. The primary endpoint of microbiological response was met at the test-of-cure (ToC) visit, which occurred 3 to 7 days after patients received treatment.
“These results highlight the potential of gepotidacin as a new oral treatment option given the rising incidence of gonorrhoea worldwide including drug resistant infections,” said Chris Corsico, SVP of Development at GSK, in a press release.
The other 2 phase 3 trials, EAGLE-2 and EAGLE-3 compared the efficacy and safety of 1500 mg of oral gepotidacin administrated twice-daily for 5 days with 100 mg of oral nitrofurantoin administered twice daily for 5 days over a 28-day duration. Both trials had the same primary endpoint of the combined clinical and microbiological response at the ToC visit—which occurred on days 10 through 13—in patients with uropathogens that are susceptible to nitrofurantoin. These results were presented at the European Congress of Clinical Microbiology and Infectious Diseases in April 2023.
The EAGLE-1 trial demonstrated safety and tolerability profiles consistent with the phase 1 and 2 trials, with the most commonly reported adverse events (AEs) among patients who received gepotidacin being gastrointestinal symptoms. Additionally, all AEs reported were mild or moderate in severity, with only 1 grade 3 AE, as well as 1 serious event in the gepotidacin arm that was unrelated to treatment.
According to the researchers, if approved by the FDA, gepotidacin could be the first oral antibiotic in uUTI treatment in over 20 years. EAGLE-1 is the third positive pivotal trial to evaluate gepotidacin.
“The imperative for innovative treatments has never been clearer. We are committed to working with health regulators globally to introduce this potential new antibiotic, focusing on solutions that meet critical patient needs,” said Corsico in the press release.
