C96-01 Zelicapavir Reduces Symptom Duration and Hospitalization in a Randomized, Double-Blind, Placebo-Controlled, International, Phase 2 Trial

Abstract Introduction RSV causes significant morbidity in young children and high-risk adults despite availability of prophylactic strategies. Zelicapavir (EDP-938) is an oral antiviral that inhibits RSV replication by acting on the N-protein. Methods A randomized, double-blind, placebo-controlled global study enrolled RSV PCR positive, symptomatic, high-risk outpatients within 3 days of symptom onset. Zelicapavir vs placebo (2:1) was administered daily for 5 days and subjects followed for 28 d. Efficacy was assessed by patient reported outcome questionnaires—the Respiratory Infection Intensity and Impact Questionnaire (RiiQ™) and the Patient Global Impression of Severity (PGI-S). Results 186 subjects were enrolled in the trial, including 142 participants at the highest risk for RSV complications, those with COPD, CHF or ≥ 75yo (HR3 population). Subjects were evenly matched on baseline characteristics. No differences were noted between zelicapavir and placebo treated subjects regarding safety measures. No adverse events lead to study drug or study withdrawal. The primary study endpoint of time to resolution of lower respiratory tract disease (LRTD) symptoms by RiiQ™ to mild or absent was not met; however, time to complete resolution, defined as all 13 RSV symptoms absent, showed an improvement of 2.2-days in the efficacy population and 6.7 days in the HR3 population. Zelicapavir treatment achieved complete resolution of the total RiiQ ™ 3.6 days faster for the efficacy population and 7.2 days faster for the HR3 population. Assessment of the PGI-S showed a 2-day faster time to improvement of symptoms in the zelicapavir treated efficacy population (p = 0.0446) as well as the HR3 population (p = 0.0465). Fewer zelicapavir treated subjects were hospitalized versus placebo. There was one RSV-related death in the study (placebo-treated). Zelicapavir resulted in a larger viral load decline in both efficacy and HR3 populations (0.6 log10 and 0.7 log10, respectively). Conclusions Treatment with zelicapavir in high-risk adult populations infected with RSV was associated with faster time to complete resolution of symptoms evaluated by the RiiQ™ and the PGI-S. Further, zelicapavir led to a reduction in hospitalization and a greater decline in RSV viral load. These results support continued investigation of zelicapavir as potential treatment for RSV in high-risk adults. This abstract is funded by: Enanta Pharmaceuticals