EDP-323, a First-In-Class, Once-Daily, Oral L-Protein Inhibitor for the Treatment of RSV: Results From a Phase 1 Study in Healthy Adults

Abstract

Respiratory syncytial virus (RSV) remains a significant health concern, particularly for vulnerable populations. Despite preventive strategies, there remains a need for effective antiviral treatments. EDP-323 is a first-in-class, potent oral selective non-nucleoside inhibitor of the large protein (L polymerase) of RSV under investigation for the treatment of RSV infection. This phase 1, randomized, double-blind, placebo-controlled study evaluated the safety and pharmacokinetics of EDP-323. This study included fasted single ascending dose (SAD; EDP-323 50/100/200/400/600/800 mg doses, 3:1 to placebo), fed multiple ascending dose (MAD; EDP-323200/400/600/800 mg doses, 3:1 to placebo), and food effect (EDP-323200 mg dose, 4:1 to placebo) cohorts in healthy adult participants. Key objectives were to assess the safety, tolerability, and pharmacokinetic (PK) profile of EDP-323 in plasma and urine, and to evaluate the effect of food intake on its pharmacokinetics. Among 82 randomized participants (SAD, n = 50; MAD, n = 32), EDP-323 was well tolerated up to the highest tested dose (800 mg once daily for 7 days). Adverse events (AEs) were reported in 14.6% of total participants, with the majority being mild and deemed unlikely related to the study drug. Headache was the most frequent AE (n = 3). PK analysis showed that EDP-323 was rapidly absorbed (T_max = 3.0-5.0 h), with exposures increasing with ascending dose. The half-life of EDP-323 (t_1/2 = 10.8-16.6 h) supported once-daily dosing, and no food effect was observed. EDP-323 demonstrated a favorable safety and PK profile, supporting its potential as a once-daily oral treatment for RSV.

Keywords: clinical trials; healthy subjects; infectious disease; oral; pharmacodynamics; pharmacokinetics; phase I; safety.

FIGURE 1

Study design. Healthy volunteers were randomized 3 (active): 1 (placebo), 4:1 in the FE cohort. All SAD participants were fasted except for those in a 200 mg FE cohort (high‐fat meal). All MAD participants were fed a standard meal. FE, food effect; MAD, multiple ascending dose; SAD, single ascending dose.

FIGURE 2

Mean EDP‐323 plasma concentration vs. time following oral administration of single doses on a linear scale (A) and log scale (B). Analysis was based on the PK set defined as all participants who received the study drug with a measurable plasma concentration of the study drug. PK, pharmacokinetic.

FIGURE 3

Mean EDP‐323 plasma concentration vs. time on Day 7 following oral administration of multiple doses on a linear scale (A) and log scale (B). Analysis was based on the PK set defined as all participants who received the study drug with a measurable plasma concentration of the study drug. PK, pharmacokinetic.