This approval of gepotidacin is the first in a new antibiotic class for the treatment of gonorrhoea approved in over 3 decades.
The FDA has approved the supplemental new drug application (sNDA) for gepotidacin (Blujepa; GSK) as an oral treatment option for uncomplicated urogenital gonorrhea in patients aged 12 years and older weighing at least 45 kg, and who have limited or no alternative options for the treatment of uncomplicated urogenital gonorrhoea caused by susceptible strains of Neisseria gonorrhoeae. The approval provides a noninjectable alternative to existing standard therapy for this sexually transmitted infection.1
Gepotidacin previously received FDA approval in March 2025 as an oral treatment for uncomplicated urinary tract infections in female adult and pediatric patients aged 12 years and older weighing at least 40 kg. Regulatory processes for that indication remain ongoing in other regions, including the United Kingdom and Australia.2
According to national surveillance data, more than 600,000 cases of gonorrhea were reported in the United States in 2023, making it the second most frequently reported sexually transmitted infection in the country. Without timely or adequate treatment, infection may result in infertility and other reproductive sequelae. There is no licensed gonorrhea vaccine in the United States, and standard therapy requires injectable administration, which may be inaccessible or unacceptable for certain patients.3
Tony Wood, chief scientific officer at GSK, said, "We're proud to have delivered the first new class of antibiotics for gonorrhoea in over three decades and a new oral option for US patients. The ability of N. gonorrhoeae to develop resistance to currently available options, including standard of care, makes it important to expand the range of effective oral treatments".
Approval of the supplemental indication was supported by findings from the phase 3 EAGLE-1 clinical trial, published in The Lancet. The study evaluated gepotidacin as a noninferior oral alternative to the current leading regimen of intramuscular ceftriaxone plus oral azithromycin. The trial enrolled participants aged 12 years and older with suspected uncomplicated urogenital gonorrhea. Participants were randomly assigned to receive 2 oral doses of gepotidacin 3000 mg administered 10 to 12 hours apart or ceftriaxone 500 mg intramuscular plus azithromycin 1 g orally.3
The primary end point was microbiological success at test-of-cure (days 4–8), defined as culture-confirmed eradication of Neisseria gonorrhoeae from the urogenital site. In the microbiological intention-to-treat population (n=406), microbiological success occurred in 92.6% (187/202; 95% CI, 88.0–95.8) of gepotidacin recipients and 91.2% (186/204; 95% CI, 86.4–94.7) of participants receiving ceftriaxone plus azithromycin, meeting the prespecified noninferiority criteria. No bacterial persistence at the urogenital site was reported in either group.
Gepotidacin demonstrated a safety and tolerability profile consistent with prior clinical experience. The most common adverse events were gastrointestinal, predominantly mild to moderate in severity. Investigators reported, “No treatment-related severe or serious adverse events occurred in either group.”
Gepotidacin is a bactericidal, first-in-class triazaacenaphthylene antibiotic that inhibits bacterial DNA replication through a novel mechanism involving a distinct binding site and, for most pathogens, balanced inhibition of 2 type II topoisomerase enzymes. The agent demonstrates activity against N gonorrhoeae and most target uropathogens, including Escherichia coli and Staphylococcus saprophyticus, including many strains resistant to current antibiotics.
According to GSK, the approval represents the second major US regulatory milestone for the agent. “The FDA’s acceptance of our application for priority review reflects the potential of gepotidacin to address a significant unmet need in gonorrhea treatment,” the company stated. The manufacturer noted that the updated approval provides a new oral option for clinicians treating this infection.
With FDA approval, gepotidacin is now the first in a new class of oral therapy available for uncomplicated urogenital gonorrhea in the United States. The availability of an oral regimen may reduce reliance on injectable therapy and support broader access to timely treatment, particularly in clinical settings where intramuscular options are impractical or unavailable. Clinicians may consider gepotidacin for eligible patients according to labeling, resistance patterns, and individual clinical circumstances.
"I think this is extremely exciting news. Antibiotic resistance to gonorrhea is a major problem worldwide and a big concern. I know it's something that keeps me up at night, and lots of questions and concerns there. And so this feels very, very hopeful, both for immediate treatment related to this medication and just thinking forward to ongoing development of new treatments," said Angela Hasler, APRN, CPNP-PC, pediatric nurse practitioner, adolescent and young adult medicine, Children’s National Hospital, Washington D.C.; NAPNAP member.
References
