At IDWeek 2025, held on 19–22 October, Dr John P DeVincenzo from Enanta Pharmaceuticals presented data from a Phase IIa human challenge study for the company’s investigational respiratory syncytial virus (RSV) therapeutic, a first-in-class once-daily, orally administered L-protein inhibitor.
EDP-323 achieved rapid, statistically significant reductions in RSV viral load and symptoms compared with placebo and was well tolerated, supporting its continued clinical development.
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The randomised, 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. Treatment was initiated approximately 12 hours after the first positive polymerase chain reaction (PCR) result or on day five post-inoculation, whichever came first. The primary endpoint was viral load area under the curve (AUC) measured by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) in the intent-to-treat infected population, with secondary endpoints including viral culture AUC, total symptom AUC, and exploratory assessment using the psychometrically validated Respiratory Infection Intensity and Impact Questionnaire (RiiQ™).
EDP-323 significantly reduced mean viral load AUC by 85% and 87% in the high- and low-dose groups, respectively, compared with placebo (p<0.0001 for both). Similarly, mean viral load measured by culture was reduced by 98% and 97%, respectively, in the high- and low-dose groups (p<0.0001 for both). 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. No statistically significant difference was observed between the two EDP-323 dosing regimens.
The antiviral effect translated to clinically meaningful symptom improvements. 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 RiiQ™ patient-reported outcome tool, total symptom AUC was reduced by 61% and 73% (p=0.0010 and p=0.0012), respectively, while lower respiratory tract disease (LRTD) symptom AUC decreased by 73% and 95% (p=0.0088 and p=0.0002), respectively. These results demonstrate consistent alignment between virologic and clinical endpoints.
Safety findings were favorable, 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.
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By GlobalDataEDP-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. DeVincenzo, 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.
These findings also 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.
Taken together, the IDWeek 2025 results indicate that EDP-323 is a promising once-daily oral candidate with rapid antiviral onset, potent efficacy, and a benign safety profile. This is highly encouraging considering 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. The results of this Phase IIa trial demonstrate that EDP-323 has strong potential to address this gap in the market. Enanta plans to advance the molecule 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.
Enanta also has another asset in Phase II development as an RSV therapeutic, the N-protein inhibitor zelicapavir, which reinforces 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. Zelicapavir demonstrated clinically meaningful reductions in symptom duration for certain patient groups and met key secondary endpoints.
