GSK plc announced that the US Food and Drug Administration (FDA) has approved a supplemental New Drug Application for gepotidacin as an oral option for adult and paediatric patients from 12 years of age weighing at least 45 kg who have limited or no alternative options for the treatment of uncomplicated urogenital gonorrhoea caused by susceptible strains of Neisseria gonorrhoeae (e.g., where standard of care is contraindicated, or where patients are intolerant or unwilling to use first line treatment). This milestone follows the US FDA approval of gepotidacin earlier this year as an oral treatment for female adult and paediatric patients 12 years of age and older (weighing =40 kg) with uncomplicated urinary tract infection (uUTI). Blujepa is the first in a new antibiotic class for the treatment of gonorrhoea approved in over three decades.
Blujepa offers a new oral option for US patients with gonorrhoea currently relying on injectable treatments. Neisseria gonorrhoeae is a priority pathogen for the World Health Organization with significant need for new treatments. The US application was based on positive results from the EAGLE-1 phase III trial which demonstrated that gepotidacin was non-inferior to standard of care combination treatment for gonorrhoea (intramuscular ceftriaxone plus oral azithromycin).
The trial also supported the safety and tolerability profile of gepotidacin, with no serious drug related adverse events observed in either the gepotidacin or the comparator arm. The most common reported adverse reactions were mild to moderate gastrointestinal events. With this approval, gepotidacin is now available to US patients for the treatment of uncomplicated urogenital gonorrhoea when appropriate.
The development of gepotidacin has been funded in part with federal funds from the US Department of Health and Human Services, Administration for Strategic Preparedness and Response, Biomedical Advanced Research and Development Authority (BARDA), under Other Transaction Agreement number HHSO100201300011C based on its potential for use against secondary bacterial infections that may arise following chemical, biological, radiological, and nuclear (CBRN) incidents and with federal funds awarded by the US Department of Defense's Threat Reduction Agency under agreement number HDTRA1-07-9-0002. Gepotidacin, discovered by GSK scientists, is a bactericidal, first-in-class triazaacenaphthylene antibiotic that inhibits bacterial DNA replication by a distinct binding site, a novel mechanism of action, and for most pathogens, provides well-balanced inhibition of two different Type II topoisomerase enzymes. This provides activity against Neisseria gonorrhoeae and most target uropathogens (such as Escherichia coli and Staphylococcus saprophyticus), including isolates resistant to current antibiotics.
Due to this well-balanced inhibition for most pathogens, a single target-specific mutation may not significantly impact gepotidacin activity. The EAGLE-1 trial (NCT04010539) is part of a comprehensive global phase III clinical programme for gepotidacin in adults and adolescents including: EAGLE-1 (non-inferiority urogenital gonorrhoea trial) enrolled approximately 600 patients with uncomplicated urogenital gonorrhoea to compare the efficacy and safety of gepotidacin (oral, two doses of 3,000mg) to intramuscular ceftriaxone (500mg) plus oral azithromycin (1,000mg). The data were presented at the congress of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) in April 2024 and published in The Lancet in April 2025.
EAGLE-2 and EAGLE-3 (non-inferiority uUTI trials) enrolled approximately 3,000 patients to compare the efficacy and safety of gepotidacin (1,500mg administered orally twice daily for five days) to nitrofurantoin (100mg administered orally twice daily for five days). The data were first presented at the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) in 2023 and published in The Lancet in February 2024.
