FDA Approves Zoliflodacin for Uncomplicated Urogenital Gonorrhea

Today, the FDA approved Innoviva Specialty Therapeutics’ zoliflodacin (Nuzolvence), a first-in-class, single-dose oral medication for the treatment of uncomplicated urogenital gonorrhea in adults and pediatric patients 12 years and older weighing at least 35 kg. This approval was based from data of a phase 3 trial, which was published in The Lancet, showing that the antibiotic was noninferior to a combination regimen of ceftriaxone and azithromycin.

“Our study demonstrated the non-inferior efficacy of zoliflodacin in uncomplicated urogenital gonorrhea compared to a very potent, two-drug regimen,” study co-author Stephanie N. Taylor, MD, professor of Medicine, Section of Infectious Diseases, Louisiana State University Health Sciences Center and Medical Director, LSU STD Research laboratory, said in a statement. “Microbiological cure rates at extragenital (pharyngeal and rectal) sites were also comparable between the two arms and both exhibited a similar safety profile.”

Phase 3 Trial Specifics and Findings

In a pivotal phase 3, multinational, randomized, controlled, open-label, non-inferiority trial, zoliflodacin demonstrated non-inferiority compared to the dual therapy of ceftriaxone plus azithromycin for the treatment of uncomplicated urogenital gonorrhea, with both treatment groups showing comparable safety profiles.

The study enrolled 930 adolescent and adult participants to evaluate the efficacy and safety of a single 3g oral dose of zoliflodacin versus a single dose of 500mg intramuscular injection of ceftriaxone plus 1g oral azithromycin for the treatment of uncomplicated gonorrhea. This trial was the largest clinical trial ever conducted for a new treatment against Neisseria gonorrhoeae infection, with 16 trial sites in regions with a high prevalence of gonorrhea across five countries, including Belgium, the Netherlands, South Africa, Thailand, and the US.¹

Study results showed that zoliflodacin was noninferior to the combination therapy (5.31%, 95% confidence interval: 1.38-8.65) with urogenital microbiological cure rates of 90.9% (88.1-93.3) and 96.2% (92.9-98.3), respectively, for the microbiological intent-to-treat population. Zoliflodacin had a favorable safety profile with comparable overall number of adverse events between the treatment arms.²

Until this week, there was only one first-line treatment option available for patients with uncomplicated urogenital gonorrhea. Earlier this year, FDA has granted zoliflodacin a Qualified Infectious Disease Product (QIDP) designation. This designation allows it to benefit from FDA Priority Review, and extended market exclusivity. ¹

“As clinicians, we are eagerly awaiting new treatments that can effectively overcome resistance and provide a single oral dosing option,” Patrik Hornak, MD, associate program director of the ID Fellowship Program and Clinical Director of the AIDS Education & Training Center Program at the University of Texas Medical Branch, said in a statement.¹

About the Agent

Zoliflodacin a first-in-class oral, single-dose antibiotic for the treatment of uncomplicated gonorrhea is in late stage clinical trials, and has demonstrated efficacy and safety. This phase 3 trial was a global, randomized, controlled study that evaluated the efficacy and safety of zoliflodacin. Zoliflodacin inhibits bacterial DNA gyrase, an essential enzyme for bacterial survival. Zoliflodacin mechanism of action is distinct from that of currently approved antibiotics and has demonstrated activity against drug-resistant Neisseria gonorrhoeae.¹

References

1. Innoviva Specialty Therapeutics Announces Publication in The Lancet of Positive Zoliflodacin Phase 3 Data for the Treatment of Uncomplicated Urogenital Gonorrhea. Innoviva press release. December 12, 2025. Accessed December 12, 2025.
https://innovivaspecialtytherapeutics.com/innoviva-specialty-therapeutics-announces-publication-in-the-lancet-of-positive-zoliflodacin-phase-3-data-for-the-treatment-of-uncomplicated-urogenital-gonorrhea/

2. Innoviva Specialty Therapeutics Presents Findings from Subgroup Analyses of zoliflodacin in uncomplicated gonorrhea at the 2024 Sexually Transmitted Infections Conference. Innoviva press release. September 19, 2024. December 12, 2025.
https://innovivaspecialtytherapeutics.com/innoviva-specialty-therapeutics-presents-findings-from-subgroup-analyses-of-zoliflodacin-in-uncomplicated-gonorrhea-at-the-2024-sexually-transmitted-infections-conference/