Edward Hook, MD, discusses FDA approval of oral zoliflodacin for uncomplicated gonorrhea

A long-awaited addition to gonorrhea treatment options

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 one of only two new treatment options approved for uncomplicated urogenital gonorrhea in nearly two decades.

Hook 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.

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

Current US guidelines recommend intramuscular ceftriaxone as first-line therapy for uncomplicated gonorrhea. Hook highlighted several limitations of this approach. “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. “It's orally available, 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.”

Clinical trial scope informing regulatory 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 four 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.

Implications for everyday clinical practice

Hook emphasized that the availability of a single-dose oral option may meaningfully change how clinicians manage suspected gonorrhea. “The fact that you only have to take 1 medication, as well as the fact that it's an oral medication, really is a nice thing for gonorrhea treatment,” he said.

He added that emerging resistance and limited treatment alternatives have created challenges that extend beyond individual patients. “Having a drug that does not require injection and can be used for patients who are allergic to penicillin or related drugs meets important unmet needs in the treatment of gonorrhea,” Hook said.

As clinicians begin to incorporate zoliflodacin into practice, ongoing experience will clarify its role alongside existing therapies in addressing both individual patient care and broader public health concerns related to antimicrobial resistance.

Disclosure

Hook reported no relevant disclosures.

Reference

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