Gepotidacin, an investigational oral antibiotic, achieved 92.6% microbiological success in treating uncomplicated urogenital gonorrhea and demonstrated noninferiority to standard injectable therapy, according to a recent study.

In a phase 3, randomized, open-label, sponsor-blinded, multicenter trial, researchers evaluated the efficacy and safety of oral gepotidacin, a novel triazaacenaphthylene antibacterial, for the treatment of uncomplicated urogenital gonorrhea. The EAGLE-1 trial (NCT04010539) enrolled participants across 49 sites in six countries and compared two oral doses of gepotidacin (3,000 mg each, administered 10 to 12 hours apart) with the standard regimen of a single intramuscular dose of ceftriaxone (500 mg) plus oral azithromycin (1 g). The primary endpoint was microbiological success—defined as culture-confirmed eradication of Neisseria gonorrhoeae from the urogenital site at the test-of-cure visit (days 4 to 8)—which was evaluated in the microbiological intention-to-treat (micro-ITT) population.

According to results published in The Lancet, a total of 628 participants aged 12 years or older were randomized to each treatment group (314 patients per group). The micro-ITT population included 406 participants—202 in the gepotidacin group and 204 in the comparator group—all with ceftriaxone-susceptible N gonorrhoeae isolates from baseline urogenital cultures. Microbiological success was achieved in 92.6% (187 of 202) of participants treated with gepotidacin and in 91.2% (186 of 204) of those treated with ceftriaxone plus azithromycin. The adjusted treatment difference was –0.1%, which met the prespecified noninferiority margin of –10%. No bacterial persistence at the urogenital site was observed in either group.

Among participants with rectal gonorrhea, microbiological success was reported in 100% (26 of 26) of those who received gepotidacin and in 80% (12 of 15) of those in the comparator group. For pharyngeal infections, microbiological success was achieved in 78% (14 of 18) with gepotidacin and 94% (16 of 17) with ceftriaxone plus azithromycin, according to Jonathan D C Ross, MD, of the Department of Sexual Health and HIV at Birmingham University Hospitals NHS Foundation Trust in Birmingham, U.K., and colleagues.

Adverse events occurred in 74% of participants who received gepotidacin compared with 33% of those who received the comparator treatment. Events were primarily gastrointestinal and mild to moderate in severity. No treatment-related serious adverse events were reported.

Researchers concluded that gepotidacin was noninferior to ceftriaxone plus azithromycin for the treatment of uncomplicated urogenital gonorrhea and noted its potential as an oral treatment option given current concerns about antimicrobial resistance.

Full disclosures can be found in the published study.