Edward Hook, MD, reacts to the FDA approval of zoliflodacin for uncomplicated urogenital gonorrhea

The FDA recently approved Nuzolvence (zoliflodacin; Innoviva Specialty Therapeutics) for the treatment of uncomplicated urogenital gonorrhea in adults and pediatric patients aged 12 years and older who weigh at least 35 kg. The product is administered as a single oral dose and represents 1 of only 2 new treatment options approved for uncomplicated urogenital gonorrhea (gepotidacin: GSK) in nearly 3 decades.^1,2

In this video interview, Edward Hook, MD, emeritus professor of Medicine, University of Alabama at Birmingham, emphasized the importance of this milestone.

“It's been many years since a new drug was approved for treatment of gonorrhea, and the treatment of zoliflodacin is a really great step forward,” he said. He noted that the prolonged absence of new therapies has coincided with steadily increasing antimicrobial resistance worldwide.

Addressing rising resistance and unmet clinical needs

Gonorrhea remains one of the most common bacterial sexually transmitted infections globally, with more than 82 million new cases estimated each year. In the United States alone, more than 500,000 cases are reported annually, with the highest burden among sexually active adolescents and young adults.¹

Hook described antimicrobial resistance as a central concern. “An inexorable development of antibiotic resistance is an inexorable process for the gonococcus,” he said. He explained that the lack of therapeutic diversity has complicated management of a disease that is often treated empirically, without real-time susceptibility data.

“A large proportion of patients with gonorrhea are treated on the basis of a syndrome or perceived risk,” Hook added. “Having a drug that they can be confident in that will be highly effective as well as well tolerated is a great advantage.”

Advantages over injectable standard of care

“Ceftriaxone requires an injection, something that almost no patients enjoy,” he said. He also noted that the drug “is related to penicillin antibiotics, which is important because over 9% of people in the United States believe that they're allergic to penicillin, and that constrains its use.”

By contrast, zoliflodacin offers an oral alternative, "which is appreciated by patients a great deal,” Hook said. He added that oral administration may allow treatment to be prescribed without requiring patients to return to a clinic for an injection, potentially improving access and adherence.

Pavel Raifeld, CEO of Innoviva, stated, “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.”

What led to zoliflodacin FDA approval?

The FDA approval was supported by data from a large, multinational phase 3 clinical trial sponsored and led by the Global Antibiotic Research and Development Partnership. Hook highlighted the breadth of the study. “The clinical trial was carried out in over 900 participants located on 4 continents across the world,” he said, adding that this design supports broad clinical relevance across diverse populations.

He also underscored the simplicity of the regimen. “In this trial, which was carried out with twice as many participants being treated with zoliflodacin as with ceftriaxone plus azithromycin, 1 antibiotic was compared to 2,” he said. The oral therapy demonstrated non-inferiority to the injectable comparator regimen, including comparable effectiveness at extragenital sites such as the rectum and oropharynx.

Zoliflodacin approved 1 day after gepotidacin

On December 11, 2025, the FDA approved gepotidacin (Blujepa; GSK) as an oral treatment option for uncomplicated urogenital gonorrhea in patients aged 12 years and older weighing at least 45 kg, and who have limited or no alternative options for the treatment of uncomplicated urogenital gonorrhoea caused by susceptible strains of Neisseria gonorrhoeae.

Approval of the supplemental indication was supported by findings from the phase 3 EAGLE-1 clinical trial, published in The Lancet. The study evaluated gepotidacin as a noninferior oral alternative to the current leading regimen of intramuscular ceftriaxone plus oral azithromycin.

Click here for more on gepotidacin.

Edward Hook reported no relevant disclosures.

References:

1. Ebert M. FDA approves Nuzolvence (zoliflodacin) for treatment of uncomplicated urogenital gonorrhea in 12 years and up. Contemporary Pediatrics. Published December 12, 2025. Accessed December 12, 2025. https://www.contemporarypediatrics.com/view/fda-approves-nuzolvence-zoliflodacin-for-treatment-of-uncomplicated-urogenital-gonorrhea-in-12-years-and-up
2. FDA. FDA Approves Two Oral Therapies to Treat Gonorrhea. FDA. December 12, 2025. Accessed December 12, 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-two-oral-therapies-treat-gonorrhea