Enanta Pharmaceuticals announced positive topline results from a Phase 2a human challenge trial of EDP-323, an oral antiviral candidate for Respiratory Syncytial Virus (RSV) infection. The study, conducted by hVIVO, demonstrated that EDP-323 was generally safe, well-tolerated, and achieved statistically significant reductions in viral load and clinical symptoms compared to placebo in healthy adults infected with RSV.
The double-blind, placebo-controlled trial involved 142 healthy adult participants inoculated with RSV. Participants were randomized into three cohorts: a high-dose group receiving 600 mg of EDP-323 once daily for five days, a low-dose group receiving a 600 mg loading dose on day one followed by 200 mg once daily for four days, and a placebo group. The primary efficacy endpoint was the area under the curve (AUC) for viral load as measured by qRT-PCR.
Key Findings from the Phase 2a Trial
EDP-323 achieved an 85-87% reduction in viral load AUC by qRT-PCR (p<0.0001) compared to placebo. Furthermore, the study showed a 97-98% reduction in infectious viral load AUC by viral culture (p<0.0001) and a 66-78% reduction in total clinical symptoms score AUC (p<0.0001) compared to placebo. There was no statistically significant difference between the high and low dose groups.
Scott T. Rottinghaus, M.D., Chief Medical Officer of Enanta Pharmaceuticals, stated, "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."
EDP-323's Mechanism and Potential Impact
EDP-323 is a novel, oral, direct-acting antiviral that selectively targets the RSV L-protein, a crucial component for viral replication. It has received Fast Track designation from the U.S. Food and Drug Administration (FDA). The favorable pharmacokinetic profile supports once-daily dosing, with mean trough plasma concentrations maintained at 16-fold (low dose) and 35-fold (high dose) above the protein-adjusted EC90 for both RSV A and B strains.
The Need for New RSV Treatments
RSV is a common respiratory virus that causes bronchiolitis and pneumonia, especially in young children and older adults. According to the Centers for Disease Control and Prevention (CDC), virtually all children in the United States are infected with RSV by the age of two. Globally, RSV results in millions of hospitalizations and tens of thousands of deaths annually. Effective oral treatments like EDP-323 could significantly reduce the burden of this disease.
Future Directions
Enanta plans to present full data from the study at a future medical conference or in a peer-reviewed publication. With two RSV candidates, EDP-323 and zelicapavir (EDP-938), in Phase 2 development, Enanta is positioned to potentially offer single-agent or combination therapies for specific patient populations. hVIVO's Chief Scientific Officer, Dr. Andrew Catchpole, highlighted the trial's depth of actionable insights, underscoring the potential of EDP-323 to positively impact global health.
