FDA Approval of Zoliflodacin: A New Era in Gonorrhea Treatment

The US FDA approved zoliflodacin (Nuzolvence; Innoviva Specialty Therapeutics) for uncomplicated urogenital gonorrhea, making it one of the first new treatments approved for this disease in nearly 2 decades. This decision addresses a critical unmet need as Neisseria gonorrhoeae increasingly exhibits resistance to traditional therapies, leaving clinicians with few effective treatment choices.^1-3

“The FDA’s approval of [zoliflodacin] marks a pivotal moment for patients and the broader healthcare community managing gonorrhea infections. For the first time in decades, both patients and their healthcare providers will have a single-dose, oral treatment option for uncomplicated urogenital gonorrhea,” said David Altarac, MD, Chief Medical Officer, Innoviva Specialty Therapeutics. “This achievement underscores our commitment to advancing innovative therapies for infectious diseases and fighting antimicrobial resistance. It highlights the strength of our development capabilities, as well as our collaboration with GARDP and the global scientific community.”¹

Gonorrhea is the second most common sexually transmitted bacterial infection worldwide, with more than 82 million new cases each year. In the United States alone, the Centers for Disease Control and Prevention (CDC) estimates that over 543,000 cases are reported each year and over 1 million incident cases occur annually. The highest rates are seen among sexually active men ages 20 to 24, though anyone who has unprotected sex can be at risk.¹

Zoliflodacin’s Novel Mechanism and Clinical Evidence

Zoliflodacin belongs to a new chemical class of spiropyrimidinetriones, which achieves its antibacterial effect by cutting off the activity of bacterial type II topoisomerase, a necessary enzyme for DNA replication and bacterial survival.^2,3 The drug works in a different way from those already on the market, offering efficacy against strains resistant to current standard treatments.

The approval by the FDA was based on evidence from a large multinational phase 3 clinical trial, one of the largest ever conducted for gonorrhea therapies.³ This open-label, randomized, non-inferiority trial directly compared a single once-daily oral dose of zoliflodacin with the standard combination of ceftriaxone plus azithromycin.^3,4 More than 900 participants from sites in Europe, Africa, Asia, and the United States were included in the trial; zoliflodacin showed results that were statistically non-inferior to the standard regimen in clearing uncomplicated urogenital infections.³

Microbiological cure rates with zoliflodacin were similar to or slightly lower than those with the injectable combination, and no major safety issues were reported during the trial.² These findings, published in The Lancet, support the profound impact of zoliflodacin on the future management of this widespread sexually transmitted infection (STI).⁴

Making Gonorrhea Treatment More Accessible

Unlike injectable antibiotics, zoliflodacin is administered as a single oral dose, which simplifies treatment delivery in both clinical and resource-limited settings.^3,4 This is particularly relevant given the barriers many patients face in accessing intramuscular therapies.² Additionally, the FDA approval includes use in adolescents aged 12 years and older, broadening the eligible patient population.^2,3

The approval also aligns with an expanded regulatory strategy that saw the FDA concurrently approve another new oral option—gepotidacin (Blujepa; GSK) for the same indication—highlighting a pivotal moment in gonorrhea therapeutics.⁵

REFERENCES

1. Innoviva Specialty Therapeutics | U.S. FDA Approves NUZOLVENCE® (zoliflodacin), a First-in-Class, Single-dose, Oral Antibiotic for the Treatment of Uncomplicated Urogenital Gonorrhea in Adults and Adolescents. Innovivaspecialtytherapeutics.com. Published December 12, 2025 Accessed December 16, 2025. https://innovivaspecialtytherapeutics.com/u-s-fda-approves-nuzolvence-zoliflodacin-a-first-in-class-single-dose-oral-antibiotic-for-the-treatment-of-uncomplicated-urogenital-gonorrhea-in-adults-and-adolescents/

2. FDA Approves Two Oral Therapies to Treat Gonorrhea. U.S. Food and Drug Administration. Published December 12, 2025. Accessed December 16, 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-two-oral-therapies-treat-gonorrhea

3. NOZOLVENCE (Zoliflodacin), First-in-Class Oral Antibiotic for Gonorrhea, Receives U.S. FDA Approval. Published December 12, 2025. Accessed December 16, 2025. https://gardp.org/nuzolvence-zoliflodacin-first-in-class-oral-antibiotic-for-gonorrhoea-receives-u-s-fda-approval/

4. 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. Published December 11, 2025. Accessed December 16, 2025. doi:10.1016/S0140-6736(25)01953-1

5. McGovern G. FDA Approves Gepotidacin for Urogenital Gonorrhea in Adult and Pediatric Patients. Published December 11, 2025. Accessed December 16, 2025. https://www.pharmacytimes.com/view/fda-approves-gepotidacin-for-urogenital-gonorrhea-in-adult-and-pediatric-patients