Innoviva Specialty Therapeutics presented compelling new data on zoliflodacin, an investigational first-in-class oral antibiotic for uncomplicated gonorrhea, at IDWeek 2025 in Atlanta. The subset analysis from the pivotal Phase 3 trial demonstrated high microbiological cure rates across multiple infection sites, including against antibiotic-resistant strains of Neisseria gonorrhoeae.
Phase 3 Trial Results Show Promise Against Resistant Strains
The oral presentation delivered on October 22 highlighted key subgroup findings from the global Phase 3 trial, revealing high microbiological cure rates across urogenital, rectal, and pharyngeal sites in infections caused by N. gonorrhoeae with a zoliflodacin minimum inhibitory concentration (MIC) of ≤0.25 μg/mL.
Among participants with urogenital infections who received zoliflodacin, ciprofloxacin-resistant strains achieved a cure rate of 96.6% (346/358; 95% CI: 94.2–98.3), while ciprofloxacin-susceptible strains demonstrated a cure rate of 97.4% (113/116; 95% CI: 92.6–99.5). According to the data presented, high cure rates remained consistent regardless of infection site.
"Findings from our analyses reinforce our initial conclusions and support the development of zoliflodacin as a potentially transformative treatment for gonorrhea, including infections caused by resistant strains," stated Dr. David Altarac, Chief Medical Officer of Innoviva Specialty Therapeutics.
Consistent Activity Across Patient Demographics
Additional poster presentations provided further evidence of zoliflodacin's broad therapeutic potential. A demographic analysis of baseline isolates from the Phase 3 trial found that while azithromycin resistance was higher in isolates from men who have sex with men (MSM), zoliflodacin MIC values were comparable across all patient groups, including females, MSM, and heterosexual men.
These findings underscore the in vitro activity of zoliflodacin across antibiotic-resistant N. gonorrhoeae from diverse patient populations, supporting its continued development as a single, oral dose treatment for uncomplicated gonorrhea.
Surveillance Data Confirms Sustained Potency
Complementary surveillance data presented in a second poster demonstrated zoliflodacin's sustained effectiveness. In vitro susceptibility testing of N. gonorrhoeae clinical isolates collected in the U.S. during 2022 confirmed that zoliflodacin potency remained consistent compared to prior surveillance years (2020–2021), including against antibiotic-resistant strains and isolates from both male and female patients.
"The results from all three presentations show that zoliflodacin mechanism of action is differentiated from fluoroquinolones with cure rates remaining high in the face of antibiotic resistance," said Dr. Sarah McLeod, Senior Director at Innoviva Specialty Therapeutics.
Novel Mechanism of Action
Zoliflodacin belongs to the spiropyrimidinetrione class and represents a first-in-class oral antibiotic currently in development as a single-dose treatment for uncomplicated gonorrhea, including strains resistant to current first-line therapies. The drug inhibits bacterial DNA gyrase, an essential enzyme for bacterial survival, with a mechanism of action distinct from currently approved antibiotics.
The global Phase 3 trial (NCT03959527) demonstrated non-inferiority when a single oral dose of zoliflodacin was compared to ceftriaxone plus azithromycin for uncomplicated urogenital gonorrhea. This trial was sponsored by the Global Antibiotic Research and Development Partnership (GARDP), Innoviva's development partner for the program.
Regulatory Status and Market Outlook
The U.S. FDA has granted zoliflodacin Qualified Infectious Disease Product (QIDP) designation, which allows for FDA Priority Review and Extended Market Exclusivity. Innoviva Specialty Therapeutics anticipates that the New Drug Application (NDA) review will proceed according to the standard process for drugs with this designation.
The drug is currently under review by the U.S. Food and Drug Administration, representing a potential new treatment option for a growing global health threat. Dr. Altarac emphasized that "achieving high and consistent cure rates across urogenital and extra-genital sites, resistance profiles, and patient demographics represents a significant opportunity to address the growing global threat of antibiotic-resistant Neisseria gonorrhoeae."
