The US Food and Drug Administration approved two oral antibiotic therapies for uncomplicated urogenital gonorrhea, marking the first new treatment options in years as antimicrobial resistance threatens current therapeutic regimens.
Nuzolvence (zoliflodacin) granules for oral solution received approval December 12 for patients aged 12 years and older weighing at least 35 kg. Blujepa (gepotidacin) tablets gained approval December 11 for the same age group with a minimum weight of 45 kg, though its use is restricted to patients with limited alternatives due to insufficient clinical safety data. Gepotidacin previously received FDA approval in March 2025 for urinary tract infections.
"These approvals mark a significant milestone for treatment options for patients with uncomplicated urogenital gonorrhea," said Adam Sherwat, MD, director of the Office of Infectious Diseases in the FDA's Center for Drug Evaluation and Research (CDER), in a press release.
Peter Kim, MD, MS, director of the CDER Division of Anti-Infectives, emphasized the clinical urgency in the same press release: "The availability of additional treatment options is of particular importance given the global rise in gonococcal drug resistance."
Current treatment guidelines recommend single-dose intramuscular ceftriaxone, a shift from earlier combination therapy with ceftriaxone injection plus oral azithromycin.
Clinical Trial Data
The zoliflodacin pivotal trial enrolled 930 patients with uncomplicated urogenital Neisseria gonorrhoeae (N gonorrhoeae) infection. Investigators randomized two-thirds of participants to receive a single 3-g dose of zoliflodacin dissolved in water. The remaining third received standard ceftriaxone-azithromycin combination therapy. Bacterial clearance at 4 to 8 days post-treatment occurred in 91% of zoliflodacin recipients vs 96% of those who received standard therapy.
The gepotidacin trial included 628 patients who were randomized 1:1 to receive either two 3,000-mg doses administered 10 to 12 hours apart or standard injectable therapy. Microbiological cure rates at 4 to 10 days were 93% in the gepotidacin arm and 91% in the standard treatment group.
Safety Profiles
Zoliflodacin's most frequent adverse events included leukopenia, headache, dizziness, nausea, and diarrhea. Animal studies demonstrated potential teratogenicity, pregnancy loss, and male fertility impairment, which necessitated contraindications for hypersensitivity and specific drug-drug interactions.
Gepotidacin's common adverse events comprised diarrhea, nausea, abdominal pain, emesis, flatulence, dizziness, loose stools, headache, fatigue, and hyperhidrosis. The drug carries warnings for QTc prolongation, acetylcholinesterase inhibition, and hypersensitivity reactions.
Both products received Fast Track, Qualified Infectious Disease Product, and Priority Review designations for the uncomplicated urogenital gonorrhea indication. The FDA granted approval to Entasis Therapeutics for Nuzolvence and GSK for Blujepa.
Source: FDA
