Enanta Pharma Announces Top-Line Results For EDP-323 In Phase 2a Study

Enanta Pharma Announces Top-Line Results For EDP-323 In Phase 2a Study

By, Admin 30 September 2024

Enanta Pharma announces top-line results for EDP-323 in phase 2a human challenge study of healthy adults infected with RSV

Overview

Enanta Pharmaceuticals Inc, a clinical-stage biotechnology company dedicated to creating best-in-class small molecule drugs for virology and immunology indications, announced positive top-line results from a phase 2a human challenge study of EDP-323 in healthy adults infected with respiratory syncytial virus (RSV). These data demonstrated that EDP-323 was generally safe and well-tolerated and achieved an 85-87% reduction in viral load area under the curve (AUC) by qRT-PCR (p<0.0001), a 97-98% reduction in infectious viral load AUC by viral culture (p<0.0001), and a 66-78% reduction of total clinical symptoms score AUC (p<0.0001) compared to placebo. EDP-323, which received Fast Track designation from the US Food and Drug Administration, is a novel L-protein inhibitor in development as a once-daily oral treatment for RSV.

Words from CEO: Enanta Pharmaceuticals

  • We are excited about these impressive data that demonstrate a rapid and sustained reduction in viral load. These results are among the strongest ever reported in an RSV challenge study, raising the high bar set by zelicapavir. The significant antiviral activity and symptom alleviation observed in this study highlight EDP-323’s potential as a safe, highly effective, direct-acting antiviral for the treatment of RSV,” said Scott T. Rottinghaus, MD and CMO of Enanta Pharmaceuticals. 
  • These EDP-323 results represent a meaningful advancement toward achieving our longstanding goal of developing new medicines to treat respiratory infections such as RSV, as there remains a substantial need for safe and effective oral treatments. Enanta has the leading portfolio of potent RSV replication inhibitors, with EDP-323, our L-protein inhibitor, and zelicapavir, our N-protein inhibitor, both in phase 2 development.” 
  • These distinct mechanisms have the potential to be developed as once-daily single agents or in combination for specific patient populations,” added Jay R. Luly, president and CEO of Enanta Pharmaceuticals.

About Phase 2a Study

  • This phase 2a study was a randomized, double-blind, placebo-controlled, human challenge study of 142 healthy adult participants inoculated with RSV. 
  • Randomized participants (n=141) received either a once-daily (QD) 600 mg dose of EDP-323 for five days [high dose, n=47], a single 600 mg loading dose on day one followed by a 200 mg once-daily (QD) dose of EDP-323 for four days [low dose, n=47], or placebo for five days [n=47]. 
  • The intent-to-treat-infected population (ITT-I) was defined as all randomized participants receiving challenge virus and at least one dose of study drug with confirmed RSV infection.

About EDP-323 Effects

  • EDP-323 demonstrated a rapid and sustained antiviral effect. 
  • A highly statistically significant reduction (p<0.0001) was observed for the primary efficacy endpoint of AUC for viral load as measured by qRT-PCR in the ITT-I population for each of the EDP-323 dosing groups as compared with placebo. 
  • Specifically, EDP-323 lowered viral load AUC by 85% in the high dose arm and 87% in the low dose arm compared to placebo. 
  • There was no statistically significant difference between the two EDP-323 dosing groups.

The Outcomes

  • A highly statistically significant reduction (p<0.0001) was observed for the secondary efficacy endpoint of AUC for infectious viral load as measured by quantitative culture in the ITT-I population for each of the EDP-323 dosing groups, with a reduction in viral culture AUC by 98% in the high dose arm and 97% in the low dose arm compared to placebo. 
  • There was no statistically significant difference between the two EDP-323 dosing groups.
  • For the secondary efficacy endpoint of AUC for total symptom score, a highly statistically significant reduction (p<0.0001) was observed in the ITT-I population for each of the EDP-323 dosing groups, with a symptom reduction of 66% in the high dose arm and 78% in the low dose arm compared to placebo. 
  • There was no statistically significant difference between the two EDP-323 dosing groups.

EDP-323: Pharmacokinetic Effects 

  • EDP-323 demonstrated favorable pharmacokinetics, supportive of once-daily dosing. 
  • Mean trough plasma concentrations were maintained at 16-fold above the protein-adjusted EC90 with the low dose, and 35-fold above the protein-adjusted EC90 with the high dose, for both RSV A and B strains.

About EDP-323 & Study: the RSV L-protein

  • EDP-323, a novel, oral, direct-acting antiviral selectively targeting the RSV L-protein, has received Fast Track designation by the US Food and Drug Administration.
  • In a phase 1 study, EDP-323 was found to be generally safe and well-tolerated in healthy subjects up to 800 mg for up to seven days, with a pharmacokinetic profile supporting once-daily dosing and all doses achieving target exposures. 
  • In addition to its phase 1 profile, EDP-323 is also supported by in vitro data demonstrating a significant reduction in RSV replication with picomolar potency in primary human bronchial epithelial cells infected with RSV A and B, and across a range of RSV clinical isolates and 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, reductions in lung immunopathology and decreases in pro-inflammatory cytokines, including IFN, TNFa, and IL1ß.

Respiratory Syncytial Virus 

  • Respiratory Syncytial Virus 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. 
  • According to the Centers for Disease Control and Prevention, virtually all children in the United States 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 hospitalized. 
  • Globally, there are an estimated 33 million cases of RSV annually in children less than five years of age, with about 3 million hospitalized and up to approximately 120,000 dying each year from complications associated with the infection. 
  • RSV represents a significant health threat for adults older than 65 years of age, with an estimated 177,000 hospitalizations and 14,000 deaths associated with RSV infections annually in the US.

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