The FDA has approved two new oral antibiotics to treat uncomplicated urogenital gonorrhea, adding options to injectable treatments for a common sexually transmitted infection. The approvals are timely, particularly as antibiotic resistance is on the rise.
On December 12, the FDA approved Nuzolvence (zoliflodacin) oral suspension granules and Blujepa (gepotidacin) tablets for adolescents and adults aged 12 and older, with weight-based criteria. Both drugs target uncomplicated urogenital gonorrhea caused by Neisseria gonorrhoeae, a localized infection in the urethra or cervix that has not spread to other parts of the body.
Nuzolvence is broadly approved for eligible adolescents and adults, while Blujepa is indicated for patients with limited or no alternative treatment options.
Rising Resistance, Limited Options
Unlike older antibiotics such as penicillin or fluoroquinolones, both treatments act on bacterial type II topoisomerase enzymes involved in DNA replication. Because their mechanisms differ from earlier antibiotic classes, they may retain activity against some strains that are resistant to other treatments.
Gonorrhea is the second most reported bacterial sexually transmitted infection in the US. The CDC reported over 600,000 cases nationwide in 2023 and estimates roughly 1 million new infections occur each year.
Symptoms can include painful urination, genital discharge and swelling. If untreated, the infection can lead to pelvic inflammatory disease, infertility and other reproductive health complications.
Current US treatment guidelines recommend a single intramuscular injection of ceftriaxone, which requires a visit to a clinic.
In November 2025, the WHO shared surveillance data showing resistance to ceftriaxone rising to about 5% in some regions, up from less than 1% several years earlier. N. gonorrhoeae is designated by the WHO as a priority pathogen due to its ability to rapidly develop antibiotic resistance.
Zoliflodacin, the active ingredient in Nuzolvence, is a small-molecule antibiotic that inhibits bacterial type II topoisomerase through a mechanism distinct from currently approved gonorrhea treatments. Gepotidacin, the active ingredient in Blujepa, also targets bacterial DNA replication by interfering with two type II topoisomerase enzymes at a novel binding site.
Related: GSK’s Blujepa Wins FDA Approval as First New Class of Antibiotic for UTIs
Clinical Trial Evidence Behind the Dual Approvals
The approval of Nuzolvence was supported by a multinational, randomized, open-label Phase III trial with 930 adolescents and adults diagnosed with uncomplicated urogenital gonorrhea in regions with high infection rates.
Participants received either a single 3 g oral dose of zoliflodacin or standard therapy, which included intramuscular ceftriaxone plus oral azithromycin. N. gonorrhoeae clearance was evaluated 4 to 8 days post-treatment. Cure rates were 91% for zoliflodacin and 96% for standard therapy, meeting the criteria for non-inferiority.
Approval for Blujepa was based on the Phase III EAGLE-1 trial, which included 628 patients. Participants received either two oral doses of gepotidacin at 3,000 mg taken 10 to 12 hours apart or standard combination therapy. Bacterial clearance was assessed 4 to 10 days after treatment, showing cure rates of 93% and 91%, respectively, also meeting non-inferiority standards.
Nuzolvence is taken as a single oral dose mixed with water, while Blujepa is taken as two oral doses on the same day.
With the gonorrhea treatment landscape, prevention strategies are also being explored. In August 2025, England began a targeted rollout of the 4CMenB meningococcal B vaccine in sexual health clinics following evidence of partial cross-protection against gonorrhea in people at highest risk.
Other oral antibiotics are also in development, including Debiopharm’s Debio 1453, which received support from CARB-X in May 2025 to advance early-stage clinical development related to gonorrhea.
Nuzolvence was developed through a partnership between Innoviva Specialty Therapeutics and the Global Antibiotic Research and Development Partnership, a nonprofit focused on creating new antibiotics. The company plans to commercialize Nuzolvence in the second half of 2026. Blujepa was developed by GSK and is already available in the US for eligible patients with uncomplicated urogenital gonorrhea.
If you want your company to be featured on Xtalks.com, please email [email protected].
Join or login to leave a comment
JOIN LOGIN