FDA Approves First-in-Class Zolifodacin for Uncomplicated Gonorrhea

The FDA has approved zoliflodacin (Nuzolvence; Innoviva Specialty Therapeutics), a first-in-class, single-dose oral therapy for uncomplicated urogenital gonorrhea in adults and pediatric patients aged 12 years and older who weigh at least 35 kg (77 lb). Zoliflodacin granules dissolve in water and offer a long-awaited oral alternative to injectable therapy.1

The approval marks 1 of 2 regulatory decisions within as many days addressing treatment of the sexually transmitted infection and represents the first new classes of gonorrhea therapies approved in nearly 2 decades, according to the FDA.2

In a separate decision announced December 11, the FDA approved gepotidacin (Blujepa) tablets from GSK for the same indication in patients aged 12 years and older weighing at least 45 kg (99 lb).3 However, gepotidacin is limited to individuals with few or no alternative treatment options, reflecting more limited clinical safety data in gonorrhea. Gepotidacin was first approved in March 2025 for uncomplicated urinary tract infections.

“These approvals mark a significant milestone for treatment options for patients with uncomplicated urogenital gonorrhea,” said Adam Sherwat, MD, director of the Office of Infectious Diseases in the FDA’s Center for Drug Evaluation and Research (CDER), in the agency’s announcement.2

According to Innoviva Specialty Therapeutics, the approval reflects a collaboration with the Global Antibiotic Research and Development Partnership, which sponsored and led the pivotal clinical trial that formed the basis for regulatory review.1

“The FDA’s approval of Nuzolvence marks a pivotal moment for patients and the broader healthcare community managing gonorrhea infections. For the first time in decades, both patients and their health care providers will have a single-dose, oral treatment option for uncomplicated urogenital gonorrhea,” Innovia CEO Pavel Raifeld, said in a statement.1

Addressing a Resistance-Driven Unmet Need

The approvals arrive amid growing concern over drug-resistant Neisseria gonorrhoeae. “The availability of additional treatment options is of particular importance given the global rise in gonococcal drug resistance,” Peter Kim, MD, MS, director of CDER’s Division of Anti-infectives, said in the FDA announcement.2

Gonorrhea remains a major global public health challenge, with more than 82 million new cases estimated worldwide each year, making it the second most common bacterial sexually transmitted infection globally, Innovia noted. In the United States, the Centers for Disease Control and Prevention estimates that more than 543,000 cases are reported annually, with the highest rates among sexually active young adults.2

Until now, US treatment guidelines have relied on intramuscular ceftriaxone as the sole recommended first-line therapy. Oral alternatives may benefit patients with needle aversion, allergies to β-lactam antibiotics, or limited access to injection-based care, while also supporting antimicrobial stewardship efforts.

Pivotal Trial Evidence Supporting Approval

The federag agency's approval of zoliflodacin was supported by a multinational, randomized, open-label phase 3 noninferiority trial enrolling 930 adolescents and adults with uncomplicated urogenital gonorrhea. Participants received either a single 3-g oral dose of zoliflodacin or ceftriaxone 500 mg intramuscularly plus azithromycin 1 g orally.1

At test of cure 4–8 days after treatment, 91% of patients receiving zoliflodacin achieved microbiological cure, compared with 96% in the comparator arm, meeting prespecified criteria for noninferiority. Microbiological cure rates at extragenital sites, including pharyngeal and rectal infections, were also comparable between treatment groups.1

“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 at Louisiana State University Health Sciences Center, said in a statement.1

The trial, conducted across 16 sites in 5 countries, represents the largest clinical study ever completed for a novel treatment targeting N gonorrhoeae, the company stated. Zoliflodacin was generally well tolerated, with adverse events comparable between treatment groups and no serious adverse events reported.

Novel Mechanism and Clinical Implications

Zoliflodacin is a spiropyrimidinetrione antibiotic that inhibits bacterial type II topoisomerase (DNA gyrase), a mechanism distinct from fluoroquinolones and other approved gonorrhea therapies. According to Innovia, this differentiation underpins its activity against drug-resistant strains of N gonorrhoeae.1

“The decades-long absence of new gonorrhea treatments, combined with rising global antibiotic resistance, has created significant challenges in managing this common but potentially serious sexually transmitted infection,” Edward W. Hook III, MD, professor emeritus of medicine at the University of Alabama at Birmingham and lead investigator of the phase 3 trial, said in the statement. “A new antibiotic that does not require injection and can be used for patients who are allergic to penicillin or related drugs meets 2 important unmet needs in the treatment of gonorrhea.”1

For clinicians, the availability of a single-dose oral therapy may simplify treatment logistics and broaden options for patients unable to receive injectable antibiotics. Postmarketing surveillance and future guideline updates will help define the role of zoliflodacin and gepotidacin in routine clinical practice.

Both zoliflodacin and gepotidacin received FDA Fast Track, Qualified Infectious Disease Product (QIDP), and Priority Review designations for the gonorrhea indication.1

References

1. US FDA Approves Nuzolvence (zoliflodacin), a first-in-class, single-dose, oral antibiotic for the treatment of uncomplicated urogenital gonorrhea in adults. News release. Innoviva Specialty Therapeutics. December 12, 2025. Accessed December 12, 2025.

2. FDA approves 2 oral therapies to treat gonorrhea. News release. FDA. December 12, 2025. Accessed December 12, 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-two-oral-therapies-treat-gonorrhea