Single-Dose Oral Antibiotic Zoliflodacin Treats Drug-Resistant Gonorrhea

Antibiotic-resistant gonorrhea may be treated with a single-dose oral medication of zoliflodacin, according to the latest data from a phase 3 trial.¹ These findings could help treat a sexually transmitted infection (STI) that affects more than 82 million people per year around the world.

Gonorrhea has been difficult to treat, as the infection has gained resistance to all current and previously used classes of antibiotics used to treat it.² Only 1 empirical treatment option remains, making the development of new treatments paramount to treating the infection. Zoliflodacin is an oral, spiropyrimidinetrione antibiotic that had previously shown promise in treating gonorrhea in phase 1 and 2 studies. This phase 3 clinical trial aimed to evaluate the use of zoliflodacin in patients who had uncomplicated urogenital gonorrhea.

A total of 17 outpatient clinics participated in the study. The clinics were located in the USA, Belgium, the Netherlands, South Africa, and Thailand. STI case management guidelines and clinical services and resources were assessed using feasibility questionnaires for each clinic. This study included participants aged 12 years and older who had signs and symptoms of urethral or endocervical gonorrhea, had a history of unprotected sexual contact in the past 2 weeks with a partner who had gonorrhea, or had a positive laboratory test that confirmed gonorrhea.

Individuals were excluded from the study if they had used moderate or strong CYP3A4 inhibitors or inducers in the past 30 days, had confirmed or suspected complicated or disseminated gonorrhea, or were pregnant or breastfeeding.

Patients received either zoliflodacin in a single dose or a comparator in a 2:1 randomized split. The study was open-label, which meant all participants, personnel, and sponsor team members knew the treatment assignment for each patient. All participants completed screening on the first day of dosing. Participants all attended visits after baseline to assess any adverse events, blood tests, and sexual history data. The primary outcome was the efficacy of the 3g dose of soliflodacin compared with the comparator through 30 days.

There were 930 participants screened between November 2019 and March 2023 and ultimately included in the analysis, of which 856 completed the study. Most of the participants were assigned male at birth (88%), and 55% were Black or African American. The mean (SD) age of the participants was 29.7 (9.4) years. South African participants made up most of the population (46%), followed by Thailand (29%). A total of 21% of the participants were living with HIV.

The microbiological cure rates in the urogenital population were 90.9% in the zliflodacin group and 96.2% in the comparator group. When excluding patients with non-assessable outcomes, the microbiological cure rate was 96.8% in the zoliflodacin group compared with 100% in the comparator group.

The microbiological cure rates in the pharyngeal group were 79.2% in the zoliflodacin group compared with 78.6% in the comparator group. The rectal group also. Had similar cure rates between the treatments, with 87.3% of the zoliflodacin group seeing a cure compared with 88.6% in the comparator group.

There were a couple of limitations to this study. The study was open-label, which may have played a factor in the results. There was a low number of women and adolescents in the population of the study.

“This trial showed efficacy of a single dose of oral zoliflodacin for treatment of uncomplicated urogenital gonorrhea,” the authors concluded. “…These data suggest a potential role for zoliflodacin as an effective oral treatment option for uncomplicated urogenital gonorrhea.”

Zoliflodacin is currently under FDA review for the treatment of uncomplicated gonorrhea with an assigned action date of December 15, 2025.³ The antibiotic was developed by Innoviva Specialty Therapeutics, Inc, in collaboration with the Global Antibiotic Research & Development Partnership. If approved, zoliflodacin would be the first new antibiotic for treating gonorrhea in a decade.⁴

References

1. 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. Lancet. Published online December 11, 2025. doi:10.1016/s0140-6736(25)01953-1
2. Gonococcal infections among adolescents and adults. CDC. Updated September 21, 2022. Accessed December 11, 2025. https://www.cdc.gov/std/treatment-guidelines/gonorrhea-adults.htm
3. FDA grants priority review for zoliflodacin new drug application for the treatment of uncomplicated gonorrhea and assigns target PDUFA date of December 15, 2025. News release. Innoviva. June 12, 2025. Accessed December 11, 2025. https://investor.inva.com/news-releases/news-release-details/fda-grants-priority-review-zoliflodacin-new-drug-application
4. Innoviva Specialty Therapeutics receives FDA new drug application acceptance for zoliflodacin, a first-in-class oral antibiotic for uncomplicated gonorrhea in adults. News release. Global Antibiotic Research & Development Partnership. June 10, 2025. Accessed December 11, 2025. https://gardp.org/innoviva-specialty-therapeutics-receives-fda-new-drug-application-acceptance-for-zoliflodacin-a-first-in-class-oral-antibiotic-for-uncomplicated-gonorrhoea-in-adults/