Infectious Disease Regulatory Watch: December Highlights

Last month, the FDA approved 2 antibiotics for uncomplicated gonorrhea: Innoviva Specialty Therapeutics’ zoliflodacin (Nuzolvence), and gepotidacin (Blujepa).

It is rare to see 2 antibiotics get FDA-approved in the same month, let alone 2 that are for the same indication. Here is some clinical data and information around the 2 antibiotics.

Zoliflodacin. The FDA approved Innoviva Specialty Therapeutics’ antibiotic, which is a first-in-class, single-dose oral medication, for the treatment of uncomplicated urogenital gonorrhea in adults and pediatric patients 12 years and older weighing at least 35 kg. This approval was based from data of a phase 3 trial, which was published in The Lancet, showing that the antibiotic was noninferior to a combination regimen of ceftriaxone and azithromycin.

In a pivotal phase 3, multinational, randomized, controlled, open-label, non-inferiority trial, zoliflodacin demonstrated non-inferiority compared to the dual therapy of ceftriaxone plus azithromycin for the treatment of uncomplicated urogenital gonorrhea, with both treatment groups showing comparable safety profiles.

The study enrolled 930 adolescent and adult participants to evaluate the efficacy and safety of a single 3g oral dose of zoliflodacin versus a single dose of 500mg intramuscular injection of ceftriaxone plus 1g oral azithromycin for the treatment of uncomplicated gonorrhea. This trial was the largest clinical trial ever conducted for a new treatment against Neisseria gonorrhoeae infection, with 16 trial sites in regions with a high prevalence of gonorrhea across five countries, including Belgium, the Netherlands, South Africa, Thailand, and the US.¹

Study results showed that zoliflodacin was noninferior to the combination therapy (5.31%, 95% confidence interval: 1.38-8.65) with urogenital microbiological cure rates of 90.9% (88.1-93.3) and 96.2% (92.9-98.3), respectively, for the microbiological intent-to-treat population. Zoliflodacin had a favorable safety profile with comparable overall number of adverse events between the treatment arms.²

Until this FDA approval, there was only one first-line treatment option available for patients with uncomplicated urogenital gonorrhea. In 2025, FDA granted zoliflodacin a Qualified Infectious Disease Product (QIDP) designation. This designation allowed it to benefit from FDA Priority Review, and extended market exclusivity. ¹

Gepotidacin. the FDA approved GSK’s antibiotic for the treatment of uncomplicated urogenital gonorrhea in patients 12 years or older (weighing ≥ 45 kg [99.2 lb]). This approval was based from data of the EAGLE-1 phase 3 trial results, which were published in The Lancet, showing that gepotidacin (oral, 2 doses of 3000 mg) was noninferior, with a 92.6% (187 of 202; 95% CI, 88.0%-95.8%) success rate at urogenital site when compared with a 91.2% (186 of 204; 95% CI, 86.4%-94.7%) success rate for intramuscular ceftriaxone (500 mg) plus oral azithromycin (1000 mg) combined therapy.²

The EAGLE-1 study was an open-label noninferiority trial examining oral gepotidacin compared with ceftriaxone plus azithromycin. Participants had to have a body weight over 45 kg, and had suspected uncomplicated urogenital gonorrhea (including mucopurulent discharge), a positive laboratory test result for Neisseria gonorrhoeae, or both. Patients were randomly allocated in a 1:1 ratio to each treatment group, stratified by sex and sexual orientation.²

The primary efficacy end point was defined as eradication of gonorrhea at test of cure (days 4-8). The noninferiority margin was prespecified at –10%. The primary outcome was assessed in the microbiological intention-to-treat population, with all participants randomly allocated to a study treatment who received at least 1 dose of their treatment and had confirmed ceftriaxone-susceptible N gonorrhoeae isolated from the baseline culture of their urogenital specimen, The Lancet authors explained.²

This is the second major indication filed in the US for gepotidacin. The antibiotic was FDA approved back in March 2025 for uncomplicated urinary tract infections (uUTIs).³

References

1.Innoviva Specialty Therapeutics Announces Publication in The Lancet of Positive Zoliflodacin Phase 3 Data for the Treatment of Uncomplicated Urogenital Gonorrhea. Innoviva press release. December 12, 2025. Accessed January 15, 2026.
https://innovivaspecialtytherapeutics.com/innoviva-specialty-therapeutics-announces-publication-in-the-lancet-of-positive-zoliflodacin-phase-3-data-for-the-treatment-of-uncomplicated-urogenital-gonorrhea/

2.Ross JDC, Wilson J, Workowski KA, et al. Oral gepotidacin for the treatment of uncomplicated urogenital gonorrhea (EAGLE-1): a phase 3 randomised, open-label, non-inferiority, multicentre study. Lancet. 2025;405(10489):1608-1620. doi:10.1016/S0140-6736(25)00628-2

3. Parkinson J. Newly FDA-approved UTI antibiotic shows high efficacy for gonorrhea treatment. Contagion. April 15, 2025. Accessed January 15, 2026.
https://www.contagionlive.com/view/newly-fda-approved-uti-antibiotic-shows-high-efficacy-for-gonorrhea-treatment