FDA approves zoliflodacin for uncomplicated urogenital gonorrhea

On December 12, 2025, the FDA approved zoliflodacin (Nuzolvence) as a single-dose oral medication for uncomplicated urogenital gonorrhea in adults and pediatric patients 12 years and older weighing at least 77 lbs, Innoviva Specialty Therapeutics announced in a news release.¹

Zoliflodacin is a spiropyrimidinetrione bacterial type II topoisomerase inhibitor that has demonstrated activity against drug-resistant Neisseria gonorrhoeae. The agent was previously granted Qualified Infectious Disease Product designation by the FDA.

"It’s been many years since a new drug was approved for treatment of gonorrhea, and the treatment of zoliflodacin is a great step forward,” said Edward W. Hook III, MD, Professor Emeritus of Medicine at the University of Alabama at Birmingham, in an interview with Urology Times'® sister brand Contemporary OB/GYN. “It has a number of advantages over the currently recommended medication, including its effectiveness against antibiotic-resistant strains of Neisseria gonorrhoeae. Zoliflodacin fills a need for gonorrhea treatment that’s been present for a number of years.”

Data on zoliflodacin

The approval is supported by data from a phase 3 trial (NCT03959527) in which zoliflodacin demonstrated non-inferior efficacy vs a standard of care (SOC) regimen of ceftriaxone plus azithromycin in patients with uncomplicated gonorrhea. The findings were recently published in The Lancet.²

In total, the open-label trial enrolled 930 adult and adolescent patients across clinical trial sites in the US, Belgium, the Netherlands, South Africa, and Thailand. Participants were randomly assigned 2:1 to either a single 3 g oral dose of zoliflodacin (n = 621) or to a single dose of 500 mg intramuscular injection of ceftriaxone plus 1 g oral azithromycin (n = 309). The mean age of participants was 29.7 years (SD, 9.4).

Overall, the trial met its primary end point by demonstrating that zoliflodacin was non-inferior to the SOC regimen regarding microbiological response at the urogenital site at the test of cure visit (6 +/- 2 days following treatment). Specifically, the microbiological cure rate was 90.9% (95% CI, 88.1 to 93.3) in the zoliflodacin arm vs 96.2% (95% CI, 92.9 to 98.3) in the ceftriaxone/azithromycin arm, representing a difference of 5.3% (95% CI, 1.4% to 8.6%) across patients in the micro-intent-to-treat (ITT) population.

Data also showed comparable outcomes on the trial’s secondary end point of microbiological response at extragenital (rectal or pharyngeal) sites. Specifically, at pharyngeal sites, the cure rate was 79.2% (95% CI, 65.9 to 89.2) in the zoliflodacin arm vs 78.6% (95% CI, 59.0 to 91.7) in the ceftriaxone/azithromycin arm (difference, -0.7%; 95% CI, -20.8 to 16.3). At rectal sites, the cure rate was 87.3% (95% CI, 78.0 to 93.8) and 88.6% (95% CI, 73.3 to 96.8), respectively (difference, 1.2%; 95% CI, -14.3 to 12.6).

The safety profiles for each regimen were also comparable. Overall, zoliflodacin was well-tolerated, with no serious adverse events reported. Treatment-emergent adverse events (TEAEs) occurred in 46.2% of patients in the zoliflodacin arm vs 46.4% of patients in the ceftriaxone/azithromycin arm. The most common TEAEs in the zoliflodacin arm included headache (10%), neutropenia (7%), and leukopenia (4%).

REFERENCES

1. FDA approves two oral therapies to treat gonorrhea. News release. US Food & Drug Administration. December 12, 2025. Accessed December 12, 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-two-oral-therapies-treat-gonorrhea

2. Luckey A, Balasegaram M, Barbee LA, et al. Zoliflodacin versus ceftriaxone plus azithromycin for treatment of uncomplicated urogenital gonorrhoea: an international, randomised, controlled, open-label, phase 3, non-inferiority clinical trial. The Lancet. doi:10.1016/S0140-6736(25)01953-1