Within just two days, the US Food and Drug Administration (FDA) approved two completely new oral antibiotics for uncomplicated urogenital gonorrhea – a historic breakthrough after decades without real innovation in this indication.
On December 11, Blujepa® (Gepotidacin) from GSK received approval, followed by Nuzolvence® (Zoliflodacin) from Entasis Therapeutics on December 12. Both active ingredients are the first representatives of entirely new drug classes and also work against multidrug-resistant strains of Neisseria gonorrhoeae, which are increasing dramatically worldwide.
Background: A Global Threat
With over 80 million new infections annually, gonorrhea is one of the most common sexually transmitted infections worldwide. If left untreated, it can lead to infertility, chronic pelvic pain, and an increased risk of HIV. Since 2010, the disease has been considered an "urgent threat" by the CDC because the previous standard therapy (a single ceftriaxone injection plus azithromycin) is increasingly failing. In many countries, resistance rates are over 50 percent. Since 2020, the CDC in the US has already recommended high-dose ceftriaxone monotherapy, but the first resistances are also emerging here.
The New Medications at a Glance
Nuzolvence® (Zoliflodacin)
- Single dose of 3 grams of granules, dissolved in water
- Approved for adults and adolescents aged 12 years and older (≥ 35 kg)
- Pivotal study with 930 patients: 91% microbiological cure (vs. 96% ceftriaxone + azithromycin) – not statistically inferior
- Most common side effects: temporary leukopenia, headache, nausea, diarrhea
- Important warnings: teratogenic in animal studies – strict pregnancy prevention required
- Fast-Track, QIDP, and Priority Review status
Blujepa® (Gepotidacin)
- Two oral doses of 3,000 mg each, 10–12 hours apart
- Approved for adults and adolescents aged 12 years and older (≥ 45 kg)
- Pivotal study with 628 patients: 93% microbiological cure (vs. 91% standard therapy)
- Most common side effects: diarrhea, nausea, abdominal pain, possible QTc prolongation
- Already approved in March 2025 for complicated urinary tract infections
- Fast-Track, QIDP, and Priority Review status
Expert Opinions
"These approvals are a milestone for the treatment of uncomplicated urogenital gonorrhea," said Dr. Adam Sherwat, director of the Office of Infectious Diseases at the FDA. "The availability of additional options is particularly important given the global rise in resistance."
Dr. Peter Kim, head of the Anti-infectives Department, adds: "We finally have real alternatives again – and they are oral, which are easier to implement in practice than injections."
Significance for Practice
- Purely oral therapy is finally possible again – crucial for low-threshold care in practices, STI clinics, and developing countries
- Both substances retain efficacy against ceftriaxone-resistant strains (in vitro data)
- New drug classes for the first time in over 40 years (topoisomerase II inhibitors)
- WHO recommendation update expected as early as 2026
Outlook
Both medications are expected to be available starting in spring 2026. The CDC plans to quickly incorporate the new substances into the updated treatment guidelines. Experts hope that the new options will slow global resistance development and make control of the gonorrhea epidemic possible again.
Source: U.S. Food and Drug Administration. “FDA Approves Two Oral Therapies to Treat Gonorrhea”. December 12, 2025.
