Promising Results For Enanta’s EDP-323 In RSV Trial: Phase 2a Study Positive

Enanta Pharmaceuticals, Inc., a biotech company specializing in innovative small molecule treatments for viral and immune-related conditions, has reported encouraging topline results from a Phase 2a study evaluating EDP-323 in healthy adults with respiratory syncytial virus (RSV). The study revealed that EDP-323 was generally safe, well-tolerated, and resulted in significant reductions in viral load: 85-87% based on qRT-PCR (p<0.0001), 97-98% through viral culture (p<0.0001), and 66-78% in clinical symptom scores (p<0.0001), all compared to placebo. EDP-323, which holds Fast Track designation from the FDA, is an L-protein inhibitor under development as a once-daily oral therapy for RSV.

Scott T. Rottinghaus, M.D., Chief Medical Officer of Enanta Pharmaceuticals, said in a statement, “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.”

Jay R. Luly, Ph.D., President and Chief Executive Officer of Enanta Pharmaceuticals, also mentioned, “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.” 

This Phase 2a study was a randomized, double-blind, placebo-controlled human challenge trial involving 142 healthy adults who were intentionally exposed to RSV. Of the participants, 141 were assigned to one of three groups: a high-dose group receiving 600 mg of EDP-323 daily for five days (n=47), a low-dose group starting with a 600 mg dose followed by 200 mg daily for four days (n=47), or a placebo group (n=47). The intent-to-treat-infected (ITT-I) population included all those who received the virus, at least one dose of the study drug, and had confirmed RSV infection.

EDP-323 produced a rapid and prolonged antiviral response. For the primary efficacy measure, which was the reduction in viral load (AUC) as determined by qRT-PCR, both dosing groups showed highly significant improvements compared to placebo (p<0.0001). The high dose group showed an 85% reduction, and the low dose group saw an 87% reduction in viral load AUC. There was no notable difference between the two dosing regimens.

Regarding the secondary efficacy endpoint, which measured infectious viral load through quantitative culture, both EDP-323 groups achieved a remarkable reduction in viral load AUC compared to placebo, with the high dose reducing it by 98% and the low dose by 97% (p<0.0001). No significant difference was observed between the two dosing groups. For symptom severity, another secondary endpoint, both EDP-323 groups experienced significant relief, with a 66% reduction in total symptoms in the high-dose group and a 78% reduction in the low-dose group (p<0.0001). Again, there was no statistical difference between the groups.

EDP-323 showed favourable pharmacokinetics suitable for once-daily administration, with trough plasma levels maintained at 16 times the protein-adjusted EC90 in the low-dose group and 35 times in the high-dose group for both RSV A and B strains. Over the course of five days of treatment and 28 days of follow-up, EDP-323 demonstrated a positive safety profile. Adverse events were comparable across all groups, and there were no reports of serious or severe side effects, or any that led to discontinuation or withdrawal from the study.