Enanta Pharmaceuticals, a clinical-stage biotechnology company dedicated to creating small molecule drugs for viral infections and liver diseases, has dosed the first subject in its Phase I clinical trial of EDP-323, a novel, oral L-protein inhibitor in development for the treatment of respiratory syncytial virus (RSV).
RSV is the most common cause of bronchiolitis (inflammation of the small airways in the lung) and pneumonia in children under one year of age in the US and a significant cause of respiratory illness in older adults and immunocompromised individuals.1 According to the Centers for Disease Control and Prevention, virtually all children in the US get an RSV infection by the time they are two years old and one to two out of every 100 children younger than six months of age with an RSV infection may need to be hospitalised.2 Globally, there are an estimated 33 million cases of RSV annually in children less than five years of age, with about three million hospitalised and up to approximately 120,000 dying each year from complications associated with the infection.3 RSV represents a significant health threat for adults older than 65 years of age, with an estimated 177,000 hospitalisations and 14,000 deaths associated with RSV infections annually in the United States.4
This randomised, double-blind, placebo-controlled, first-in-human Phase I study will enroll approximately 80 healthy subjects ranging in age from 18 to 65 years old to evaluate the safety, tolerability and pharmacokinetics of EDP-323 with a single-ascending dose (SAD) phase, including a two-part food-effect (FE) cohort, and a multiple-ascending dose (MAD) phase.
All SAD and MAD cohorts will enroll eight participants who will be randomised to receive EDP-323 or placebo in a 3:1 ratio. The SAD/FE cohort will enroll 10 subjects randomised in a 4:1 ratio.
EDP-323 is supported by in vitro data demonstrating a significant reduction in RSV replication with picomolar potency in primary human bronchial epithelial cells against RSV A and B, with consistent potency across a range of RSV clinical isolates in various cell types.
In a mouse model of RSV infection, EDP-323 treatment was associated with dose-dependent decreases in viral load in the lung, reduced lung immunopathology and decreases in pro-inflammatory cytokines, including IFNγ, TNFα, and IL1β. Additionally, EDP-323 has favorable oral bioavailability with good plasma exposures across preclinical species and pharmacokinetic properties supporting once-daily oral dosing in humans. These data indicate that EDP-323 is a potent inhibitor of RSV replication and has the potential to be a best-in-class, broad spectrum, once daily, oral antiviral treatment for RSV.
“This first-in-human study of EDP-323, our selective, direct-acting antiviral specifically targeting the RSV L-protein, is an important milestone for Enanta as we mark the continued expansion of our clinical RSV portfolio. Compelling preclinical data show that EDP-323 potently blocks RSV replication and pathology across all RSV genotypes positioning EDP-323 as a potentially best-in-class potent oral antiviral treatment for RSV,” said Scott Rottinghaus, M.D., Senior Vice President and Chief Medical Officer of Enanta Pharmaceuticals. “EDP-323 could be used as a monotherapy or in combination with other RSV mechanisms, such as EDP-938, to broaden the addressable patient populations or treatment windows. As we continue to build upon our leadership in the RSV space, we believe having two unique mechanisms to treat the virus could potentially provide additional benefit to patients.”
- Centers for Disease Control & Prevention – Respiratory Syncytial Virus
- Centers for Disease Control & Prevention – RSV in Infants and Young Children
- Shi et al. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study. Lancet. 2017 Sep 2; 390(10098): 946–958:
- Falsey AR, et al. Respiratory syncytial virus infection in elderly and high-risk adults. New Engl J Med. 2005;352(17):1749-59.