FDA Approves Nuzolvence (Zoliflodacin): First-in-Class Oral Antibiotic for Gonorrhoea

The U.S. Food and Drug Administration (FDA) has approved Nuzolvence (zoliflodacin) granules for oral suspension for the treatment of uncomplicated urogenital gonorrhea caused by Neisseria gonorrhoeae. Approved on December 12, 2025, Nuzolvence becomes the first antibiotic from a new chemical class for gonorrhea in several decades, addressing the growing global threat of antimicrobial resistance.

Nuzolvence is administered as a single oral dose, offering an alternative to injectable regimens currently used as standard of care. The approval is limited to confirmed or suspected bacterial infections, in line with FDA guidance to reduce the risk of resistance development.

About Nuzolvence

Nuzolvence is indicated for adults and pediatric patients aged 12 years and older who weigh at least 35 kg (77 pounds). It is supplied as water-dissolving granules for oral suspension.

Zoliflodacin belongs to the spiropyrimidinetrione class of antibiotics and works by inhibiting bacterial type II topoisomerases, including DNA gyrase and topoisomerase IV. These enzymes are essential for bacterial DNA replication and cell division. This mechanism is distinct from fluoroquinolones and other existing antibiotics, reducing the likelihood of cross-resistance and supporting activity against multidrug-resistant N. gonorrhoeae strains.

Commenting on the approval, David Altarac, M.D., Chief Medical Officer of Innoviva Specialty Therapeutics, described it as a significant milestone, highlighting the availability of a new oral option after decades without innovation in gonorrhea treatment and emphasizing the role of collaboration with the Global Antibiotic Research and Development Partnership (GARDP).

Phase 3 Clinical Trial Data

The FDA approval was supported by a multinational, randomized, open-label Phase 3 non-inferiority trial conducted by GARDP in collaboration with Innoviva Specialty Therapeutics. The study compared a single 3 g oral dose of zoliflodacin with the standard regimen of ceftriaxone plus azithromycin for the treatment of uncomplicated urogenital gonorrhea.

The trial enrolled 930 participants across 16 sites in five countries: Belgium, the Netherlands, South Africa, Thailand, and the United States. The study population included women, adolescents, and people living with HIV, making it the largest pivotal trial conducted to date for a new gonorrhea therapy.

Zoliflodacin met its primary endpoint of microbiological cure, demonstrating non-inferiority to the comparator regimen. The adjusted treatment difference was 5.31% (95% CI: 1.38 to 8.65), remaining within the FDA-specified non-inferiority margin.

Extragenital Efficacy and Subgroup Outcomes

Secondary endpoints included microbiological cure at extragenital sites, which are traditionally more difficult to treat. Cure rates for rectal gonorrhea were 87.3% with zoliflodacin compared with 88.6% in the comparator group. For pharyngeal infections, cure rates were 79.2% versus 78.6%, respectively, confirming non-inferiority at these sites.

Efficacy was consistent across key subgroups, including adolescents and individuals living with HIV.

Safety Profile

Nuzolvence demonstrated a favorable safety profile. Treatment-emergent adverse events occurred in 46.2% of patients receiving zoliflodacin and 46.4% of those receiving ceftriaxone plus azithromycin. No treatment-related serious adverse events or deaths were reported.

Most adverse events were mild to moderate, with the most common including headache (10%), neutropenia (7%), leukopenia (4%), dizziness, nausea, and diarrhea.

Edward W. Hook III, M.D., Professor Emeritus at the University of Alabama at Birmingham and lead investigator of the Phase 3 trial, noted that zoliflodacin demonstrated comparable efficacy to injectable therapy while offering the convenience of oral administration, which may simplify treatment and improve access.

Regulatory and Commercial Outlook

Innoviva Specialty Therapeutics holds U.S. marketing rights for Nuzolvence and submitted the New Drug Application to the FDA in partnership with GARDP. Commercial launch in the United States is planned for the second half of 2026, with potential commercialization partners under consideration.

GARDP is also supporting global access initiatives, including regulatory filings in Thailand and South Africa, to expand availability in regions with high disease burden.

Public Health Context

According to the World Health Organization (WHO), an estimated 82.4 million new gonorrhea infections occur each year globally among adults aged 15–49 years, making it one of the most common sexually transmitted infections worldwide. Untreated gonorrhea can lead to serious complications, including infertility, pelvic inflammatory disease, ectopic pregnancy, and increased risk of HIV transmission.

Rising resistance to existing therapies, including declining susceptibility to ceftriaxone reported in some surveillance regions, has enhanced concern over future treatment options. In this context, the approval of zoliflodacin introduces a novel oral mechanism that may help preserve and diversify the therapeutic arsenal against drug-resistant gonorrhea.