646. Subgroup Analyses of Microbiological Cure Rates by Baseline Zoliflodacin MIC and Susceptibility to Ciprofloxacin in Participants from the Global Zoliflodacin Phase 3 Randomized Controlled Trial

Abstract Background Zoliflodacin (ZFD) is a first-in-class spiropyrimidinetrione gyrase inhibitor with a novel mode of action and in vitro activity against multidrug-resistant Neisseria gonorrhoeae. In a global randomized controlled Phase 3 trial, a single oral dose of ZFD demonstrated noninferiority compared to dual therapy of ceftriaxone and azithromycin for treatment of uncomplicated urogenital gonorrhea in the primary (micro-ITT) analysis set. Cure rates for extragenital infections were comparable between treatment arms. Here, subgroup analyses of microbiological cure rates by baseline ZFD MIC and susceptibility to ciprofloxacin (CIP) are presented. Methods Microbiological cure was determined by culture from urogenital, rectal and pharyngeal sites at Test of Cure (TOC; Day 6±2) in the Evaluable population (patients with a positive baseline N. gonorrhoeae culture and a culture result at TOC). Susceptibility of baseline N. gonorrhoeae isolates was determined by agar dilution following CLSI guidelines. Data were analyzed by anatomical site, treatment arm, MIC of ZFD, CIP susceptibility, geographical location, and sex assigned at birth. Results Baseline N. gonorrhoeae isolates from participants treated with ZFD had ZFD MICs of ≤ 0.008-0.5 µg/mL. For urogenital, rectal and pharyngeal sites combined, microbiological cure rates were high at ZFD MICs ≤ 0.25 µg/mL (Table 1). There were too few isolates with a MIC of 0.5 µg/mL (n=3) to infer a relationship between this MIC and cure rate. Microbiological cure rates at urogenital sites of infection for participants treated with ZFD were 96.6% (346/358; CI: 94.2-98.3) for patients with CIP-resistant and 97.4% (113/116; CI: 92.6-99.5) for CIP-susceptible baseline N. gonorrhoeae (Table 2). High rates of microbiological cure for CIP-resistant N. gonorrhoeae were maintained for pharyngeal and rectal sites of infection, geographical location and sex at birth. Conclusion High rates of microbiological cure were observed in participants who received a single, oral dose of ZFD and had baseline isolates with ZFD MICs ≤ 0.25 µg/mL or that were CIP-resistant, regardless of anatomical site of infection, geographical location and sex assigned at birth. These results support the continued development of ZFD for the treatment of uncomplicated gonorrhea. Disclosures All Authors: No reported disclosures