Gepotidacin potential novel oral treatment option for uncomplicated gonorrhoea: EAGLE-1 phase III trial shows

British drugmaker GSK announced that its investigational oral antibiotic for uncomplicated gonorrhoea met its primary efficacy endpoint in the trial. The results are based on a primary endpoint of microbiologic response at the test-of-cure visit 3 to 7 days after treatment.

The trial met its primary efficacy endpoint, with gepotidacin (oral, two doses of 3,000mg) demonstrating non-inferiority to intramuscular (IM) ceftriaxone (500mg) plus oral azithromycin (1,000mg), a leading combination treatment regimen for gonorrhoea. The company said the safety and tolerability of gepotidacin was consistent with results from earlier trials.

Gepotidacin is a late-stage antibiotic in GSK’s industry-leading infectious diseases portfolio that inhibits bacterial DNA replication, which is also in development for uncomplicated urinary tract infections (uUTI).

“With rising incidence rates and concern around growing resistance to existing treatments, gonorrhoea poses a threat to public health globally, Chris Corsico, GSK's senior vice president for development, said 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."

Gonorrhoea is a sexually transmitted infection caused by bacteria known as Neisseria gonorrhoea. 82 million new cases are estimated globally each year. Gonorrhoea affects both women and men and can lead to infertility and other sexual and reproductive health complications if left untreated or inadequately treated. It also raises the risk of HIV infection.

The tolerability and safety profile of gepotidacin in the EAGLE-1 phase III trial was consistent with findings in gepotidacin phase I and II trials.

According to company officials, the detailed findings from the EAGLE-1 trial will be presented at an upcoming scientific meeting and shared with global health authorities.

Positive phase III data from the EAGLE-2 and EAGLE-3 trials were presented at the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) in Copenhagen in April 2023 and subsequently published in The Lancet. Gepotidacin could be the first in a new class of oral antibiotics in uUTI in over 20 years if approved.

EAGLE-1 (non-inferiority urogenital gonorrhoea trial) compared the safety and efficacy of gepotidacin to ceftriaxone plus azithromycin in about 600 patients with uncomplicated urogenital gonorrhoea caused by Neisseria gonorrhoeae.

EAGLE-2 and EAGLE-3 (non-inferiority uUTI trials) compared the safety and efficacy of gepotidacin (1,500mg administered orally twice daily for five days) to nitrofurantoin (100mg administered orally twice daily for five days). Across both trials, the duration for participants was approximately 28 days, and the primary endpoint was the combined clinical and microbiological response at the ToC visit (days 10-13) in patients with qualifying uropathogens susceptible to nitrofurantoin.