The U.S. Food and Drug Administration announced this morning that it had approved the drug gepotidacin (brand name Blujepa) for the treatment of uncomplicated urogenital gonorrhea. The application was submitted by the multinational pharmaceutical and biotechnology company GSK, which developed the drug. The lab of Neil Osheroff, the John Coniglio Professor of Biochemistry in the School of Medicine Basic Sciences, provided all the mechanism of action data for GSK’s FDA application.
Gepotidacin is a first-in-class antibacterial drug. Today’s approval is Blujepa’s second FDA approval this year: It was approved in March 2025 for the treatment of uncomplicated urinary tract infections in female adults and pediatric patients 12 years of age and older. Blujepa was the first new antibacterial class approved for the treatment of uUTIs in nearly 30 years and is the first new antibacterial class approved against gonorrhea since the 1990s. The Osheroff lab also provided all of the mechanistic data critical for GSK’s previous FDA application for the use of gepotidacin against uUTIs.
Osheroff’s mechanistic insights, part of the FDA application that was approved today, were published in ACS Infectious Diseases in October and described the effects of gepotidacin on the activities of its targets, the type II topoisomerases, gyrase and topoisomerase IV, from Neisseria gonorrhoeae (the causative agent of gonorrhea). Topoisomerases are designed to cleave DNA, remove knots, tangles, and torsional tension from the genetic material, and put it back together, leaving it unscathed. In the presence of the drug, the enzymes are unable to put the DNA back together, leading to breaks in the DNA that compromise the genetic integrity of the bacterium and that eventually result in its death.
The Osheroff lab found that gepotidacin displays well-balanced dual-targeting of gyrase and topoisomerase IV in N. gonorrhoeae, which suggests that the bacterium would require mutations in both enzymes to overcome its susceptibility to the drug, predicting a low propensity for the development of target-mediated resistance.
“Currently, around 30–35 percent of clinical gonorrhea isolates in the U.S. are fluoroquinolone resistant, but the percentage of resistant strains is as high as 85–95 percent in other parts of the world,” Osheroff said. Fluoroquinolones, antibiotics that once served as first-line treatments for gonorrhea, primarily target gyrase (and not topoisomerase IV) in N. gonorrhoeae, but were removed from treatment guidelines in 2006 due to increasing levels of target-mediated resistance.
The mechanistic investigation was led by former Ph.D. students Alexandria Oviatt, PhD’22, and Jessica Collins, PhD’24, and current postdoctoral scholar Chelsea Mann. “Our findings differentiate gepotidacin’s targeting and mechanism from those of fluoroquinolones and highlight the drug’s potential to combat drug-resistant gonorrhea,” Osheroff said. “The trainees in my research group did an outstanding job with their research and I am very proud of them.”
The FDA’s approval of GSK’s Blujepa hinged not only on the mechanistic data, but on the positive results seen in a phase III clinical trial. That study, which tested the drug against a cocktail of two other antibiotics, demonstrated that gepotidacin was non-inferior to the antibiotic cocktail and showed no new safety concerns—critical clinical outcomes that all but ensured its FDA approval.
N. gonorrhoeae is transmitted sexually and causes a high health care and economic burden. According to the World Health Organization, it led to approximately 82 million new infections in people aged 15–49 years old in 2020. If untreated, gonorrhea can lead to complications that include chronic pelvic pain, ectopic pregnancy, infertility, and blindness in babies infected by their mothers around birth. Although gonorrhea is preventable and curable, the emergence of antibiotic-resistant strains of N. gonorrhoeae has led the WHO to issue a dire warning that the infection has the potential to join hepatitis B, herpes, human papillomavirus, and HIV/AIDS as incurable sexually transmitted infections.
Blujepa’s approval will provide patients with uncomplicated gonorrhea with an additional, potent tool to fight their infection.
Go deeper
The paper “Mechanism of Action of Gepotidacin: Well-Balanced Dual-Targeting against Neisseria gonorrhoeae Gyrase and Topoisomerase IV in Cells and In Vitro” was published in ACS Infectious Diseases in October 2025.
Funding
This research used funds from the National Institutes of Health and the United States Department of Veterans Affairs.