Zelicapavir Shortens RSV Symptoms but Misses Primary End Point

Zelicapavir (Enanta Pharmaceuticals), an oral once-daily inhibitor of the respiratory syncytial virus (RSV) N-protein, shortened time to complete and sustained resolution of RSV symptoms by up to 1 week in high-risk adults.¹ The antiviral did not, however, improve time to resolution of symptoms to mild or absent, the trial's primary end point. Christopher E. Harris, MD, senior medical director at Enanta, presented the phase 2 data at IDWeek 2026, held October 21-24 in Washington, DC.¹

Adults with congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), or asthma, and those older than 65 years, face elevated risk of severe RSV disease.¹ No RSV antiviral had previously shown efficacy in this population, according to the investigators. The trial enrolled outpatients, and zelicapavir was given orally for 5 days.^1,2

"This represents the first time an RSV antiviral treatment has demonstrated a clinically meaningful benefit in these high-risk adult outpatients," Scott T. Rottinghaus, MD, chief medical officer of Enanta Pharmaceuticals, said in a statement issued in September, upon the announcement of the topline data.²

Zelicapavir Phase 2 Trial Design and Primary End Point Results

In the global, randomized, double-blind, placebo-controlled trial, 186 symptomatic adults with CHF, COPD, or asthma, or older than 65 years, received zelicapavir (n = 121) or placebo (n = 65) once daily for 5 days. Participants enrolled within 3 days of symptom onset. A predefined higher-risk population with CHF, COPD, or age older than 75 years (HR3) made up 81% of the efficacy population.¹

The primary end point measured time to resolution of lower respiratory tract disease symptoms to mild or absent on the RiiQ patient-reported outcome tool, and zelicapavir showed no effect on this measure. In a predefined analysis requiring all RiiQ RSV symptoms to be absent at 2 consecutive time points, zelicapavir shortened time to complete resolution by up to 1 week. Time to sustained resolution, in which symptoms became absent and stayed absent, improved by a similar margin.¹

The gap between end points reflects how resolution was defined. Under the primary end point, symptoms rated mild counted as resolved, whereas the complete and sustained analyses required every symptom to be absent.¹ Secondary end points included Patient Global Impression of Severity (PGI-S), hospitalization, virologic measures, pharmacokinetics, and safety.¹

The investigators assessed sustained resolution because RSV causes prolonged disease in high-risk adults.¹ PGI-S scores resolved 2 days faster with zelicapavir than with placebo in both the efficacy population (P = .0446) and the HR3 population (P = .0465).¹

Hospitalization, Viral Load, and Safety Outcomes With Zelicapavir in High-Risk Adults

All-cause hospitalization occurred in 1.7% of patients receiving zelicapavir vs 5.0% of those receiving placebo. At the end of treatment, 23.5% of the zelicapavir group had undetectable viral load compared with 10.0% of the placebo group in the efficacy population (P = .0198).¹

Zelicapavir shortened median time to undetectable viral load by 4 to 5 days. It also produced a 0.6 to 0.7 log greater decline in viral load at the end of treatment in the efficacy and HR3 populations, respectively. Target drug exposures exceeded the 90% effective concentration by 55- to 57-fold, and adverse events were similar between the zelicapavir and placebo groups.¹

Results in the HR3 population, which made up most of the efficacy analysis, tracked the overall findings.¹ In this higher-risk group, zelicapavir produced a 0.7 log greater viral load decline at the end of treatment and faster PGI-S resolution than placebo (P = .0465).¹

Enanta first reported topline data from the trial, known as RSVHR, in September 2025, describing 800-mg daily dosing for 5 days in outpatients enrolled within 72 hours of symptom onset.² The company also stated it had identified multiple potential registrational end points for a phase 3 trial.²

The investigators concluded the reductions in symptom duration, hospitalization, and viral load support further development of zelicapavir.¹

References

1. Harris CE, DeVincenzo J, Chen S, et al. Zelicapavir decreases time to complete RSV symptom resolution, hospitalization and viral load in a global, randomized, double-blinded, placebo-controlled phase 2 trial of high-risk adults. Presented at: IDWeek 2026; October 21-24, 2026; Washington, DC. Poster P-3.

2. Enanta Pharmaceuticals reports positive topline results from its phase 2b study of zelicapavir for the treatment of respiratory syncytial virus (RSV) in high-risk adults. News release. Enanta Pharmaceuticals; September 29, 2025. Accessed October 22, 2026. https://ir.enanta.com/node/13321/pdf