LB6. EDP-938, a Novel RSV N-Inhibitor, Administered Once or Twice Daily Was Safe and Demonstrated Robust Antiviral and Clinical Efficacy in a Healthy Volunteer Challenge Study

BACKGROUND: Respiratory syncytial virus (RSV) represents an important global health challenge with significant morbidity and mortality in infants, elderly, and immunocompromised adults. No effective therapy is currently available. EDP-938 demonstrates potent in vitro activity against RSV Subtypes A and B. We report data from EDP 938-101, a double-blind, placebo-controlled, Phase 2a study that evaluated EDP-938 in adult volunteers inoculated with RSV-A Memphis 37b. METHODS: Subjects were healthy volunteers, 18–45 years, who were sero-suitable (i.e., lower 25th percentile). After RSV inoculation on Study Day 0, subjects had 12 hourly nasal wash monitored for RSV infection by qualitative RSV RT–PCR. On Study Day 5 or previously if qualitative RT–PCR was RSV+, subjects were randomized to receive 5 days of EDP-938 600 mg once daily (QD arm) or 500 mg loading dose then 300 mg twice daily (BID arm), or placebo twice daily. Assessments included 12 hourly nasal wash for quantitative RSV viral load, 8 hourly RSV Total Symptom Scoring (TSS) and daily mucus weights. Safety assessments were continued though Day 28 (last follow-up). The primary endpoint was the RSV viral load area under the curve (AUC) from first dose through Day 12 among RSV-infected subjects, defined as the Intent To Treat-Infected (ITT-I) population. The study was fully powered for both RSV viral load and TSS endpoints. RESULTS: A total of 115 subjects were randomized and inoculated; 86 were included in the ITT-I analysis. The primary and secondary efficacy endpoints were achieved with high statistical significance in QD and BID arms (figure and table). Among EDP-938 recipients all adverse events (AEs) were mild except for a single AE of moderate dyspepsia in the BID arm and events of moderate headache (n = 2) and hypoacusis (n = 1) in the placebo arm. All AEs resolved in follow-up. CONCLUSIONS: In the RSV Challenge study, EDP-938 administered once or twice daily achieved primary and key secondary endpoints with robust reductions in RSV viral load (by both qRT–PCR and plaque assays), symptom scores and mucus weights. These data support the further clinical evaluation of EDP-938 in populations at risk of severe RSV disease. [Image: see text] [Image: see text] DISCLOSURES: Eoin Coakley, MD, Enanta Pharmaceuticals (Employee), Alaa Ahmad, PhD, Enanta Pharmaceuticals (Employee), Kajal Larson, PhD, Enanta Pharmaceuticals (Employee), Ty McClure, PhD, Enanta Pharmaceuticals (Employee), Kai Lin, PhD, Enanta Pharmaceuticals (Employee), Kursten Tenhoor, n/a, Enanta Pharmaceuticals (Consultant), Kingsley Eze, n/a, hVIVO Services Ltd. (Employee), Nicolas Noulin, PhD, No financial relationships or conflicts of interest, Veronika Horvathova, MBChB, MSc, hVIVO Services Limited (Other Financial or Material Support, Employed by hVIVO during the conduct of the study), Bryan Murray, MBBS, No financial relationships or conflicts of interest, Mark Baillet, PhD, S-CUBED (Employee), Julie Mori, PhD, hVIVO (Employee, Shareholder) Nathalie Adda, MD, Enanta Pharmaceuticals (Employee).