Enanta Pharmaceuticals has reported breakthrough results for EDP-323, its investigational respiratory syncytial virus (RSV) therapeutic, demonstrating rapid and potent antiviral activity in a Phase IIa human challenge study presented at IDWeek 2025. The first-in-class, once-daily oral L-protein inhibitor achieved statistically significant reductions in both viral load and symptoms, positioning it as a potential game-changer in RSV treatment.
Robust Clinical Efficacy in Human Challenge Study
The randomized, double-blind, placebo-controlled study (NCT06170242) evaluated EDP-323 in 141 healthy adults aged 18-55 years who were intranasally inoculated with the RSV-A Memphis 37b strain. Participants were randomized 1:1:1 to receive either 600mg of EDP-323 once daily for five days, a low dose of 200mg once daily for four days following a 600mg loading dose, or placebo.
EDP-323 significantly reduced mean viral load area under the curve (AUC) by 85% and 87% in the high- and low-dose groups, respectively, compared with placebo (p<0.0001 for both). The antiviral effect was even more pronounced when measured by viral culture, with reductions of 98% and 97% in the high- and low-dose groups (p<0.0001 for both). Notably, the antiviral effect was evident as early as 12 hours after the first dose, marking one of the fastest onsets of activity observed in the RSV antiviral space.
Clinically Meaningful Symptom Improvements
The robust antiviral activity translated to significant clinical benefits. EDP-323 reduced mean total symptom AUC by 66% in the high-dose group and 78% in the low-dose group compared with placebo (p<0.0001 for both). Using the psychometrically validated Respiratory Infection Intensity and Impact Questionnaire (RiiQ™), total symptom AUC was reduced by 61% and 73% (p=0.0010 and p=0.0012), respectively.
Lower respiratory tract disease (LRTD) symptoms showed particularly impressive improvements, with AUC decreases of 73% and 95% (p=0.0088 and p=0.0002) in the high- and low-dose groups, respectively. These results demonstrate consistent alignment between virologic and clinical endpoints, underscoring the therapeutic potential of L-protein inhibition.
Favorable Safety Profile Supports Continued Development
Safety findings were encouraging, with treatment-emergent adverse events (TEAEs) occurring at similar rates between the EDP-323 and placebo groups (26.6% vs 27.7%). All events were mild or moderate, and no serious TEAEs, discontinuations, or deaths were reported. Only two cases of Grade 1 diarrhea were considered related to treatment. The overall safety profile mirrored placebo and was consistent with data from earlier Phase I studies.
Differentiated Mechanism and Therapeutic Potential
EDP-323 is a non-nucleoside, direct-acting inhibitor of the RSV L-protein, which is responsible for viral RNA replication and transcription. Unlike fusion inhibitors that must be administered shortly after infection to maintain efficacy, EDP-323 maintained antiviral activity even when treatment was delayed for up to three days post-inoculation in preclinical models. This pharmacologic flexibility, coupled with its high selectivity for RSV-A and RSV-B and a strong barrier to resistance, positions EDP-323 as a differentiated candidate in the RSV antiviral landscape.
According to Dr. John P DeVincenzo from Enanta Pharmaceuticals, who presented the data, "the magnitude and speed of viral suppression observed with EDP-323 are unprecedented for an RSV antiviral." He noted that the consistency between molecular, virologic, and clinical outcomes underscores the therapeutic potential of L-protein inhibition in managing RSV infections.
Dual Therapeutic and Preventive Potential
The findings build on earlier data from Enanta's ongoing analyses, which showed a marked reduction in RSV infection rates in a post-exposure prophylaxis sub-analysis. In that dataset, 0% of participants who received EDP-323 after exposure became infected, compared with 26% of those on placebo, suggesting the drug could have preventive as well as therapeutic utility.
Addressing Critical Unmet Medical Need
The results are particularly significant given the strong unmet need for novel therapeutics within the RSV space. While there have been notable breakthroughs in terms of RSV prophylaxis in recent years, treatment options remain very limited, and care is mostly supportive. The broad-spectrum antiviral ribavirin is rarely used due to modest efficacy, delivery complexity, and safety concerns.
Enanta plans to advance EDP-323 into Phase IIb trials in broader and higher-risk adult populations. If further studies are successful, EDP-323 could emerge as the leading oral antiviral option to complement current vaccine and monoclonal antibody strategies for RSV management.
The company also has another asset in Phase II development as an RSV therapeutic, the N-protein inhibitor zelicapavir, reinforcing its status as a key emerging company in this space. Although Enanta reported in September 2025 that a Phase IIb study of zelicapavir missed its primary endpoint, this drug remains in active development and demonstrated clinically meaningful reductions in symptom duration for certain patient groups.
