Written By: Divyanjali Godage BPharm
Reviewed By: Pharmacally Editorial Team
Enanta Pharmaceuticals recently announced highly encouraging Phase 2b clinical trial results for zelicapavir, an investigational oral antiviral drug, in treating respiratory syncytial virus (RSV) infection in high-risk adult outpatients. This is a promising development in the field of antiviral therapy, as currently no approved antiviral treatments are available for RSV in high-risk adult populations, who often face serious complications. Zelicapavir demonstrated significant clinical benefits, including faster symptom resolution and reduced hospitalization rates, positioning it as a potential breakthrough therapy for this vulnerable group.
About Zelicapavir
Zelicapavir is a novel small molecule N-protein inhibitor designed to inhibit RSV replication by targeting a key viral protein necessary for viral assembly and propagation. It is administered orally once daily, offering a convenient treatment option. Zelicapavir has received Fast Track designation from the U.S. FDA due to its potential to address the unmet need in RSV therapy. Prior studies, including a Phase 2 pediatric study and a human challenge study in healthy adults, have shown promising antiviral activity and a favorable safety profile, supporting its continued clinical development.
About RSV
Respiratory syncytial virus (RSV) is a common, highly contagious respiratory virus that infects the lungs and airways, causing symptoms similar to a cold but with the potential for severe illness in infants, older adults, and people with chronic heart or lung diseases. RSV is a major cause of lower respiratory tract infections, bronchiolitis, and pneumonia, especially in high-risk groups. Infection typically leads to symptoms including cough, wheezing, shortness of breath, and nasal congestion. Severe cases may require hospitalization, and no antiviral drugs are currently approved for high-risk adults.
Study Design and Endpoints
The Phase 2b trial, known as RSVHR, was a randomized, double-blind, placebo-controlled study enrolling outpatient adults at high risk for RSV complications such as elderly patients (≥75 years), and those with chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), or asthma. Participants were treated within 72 hours of symptom onset with either 800 mg of zelicapavir or placebo once daily for five days.
The trial assessed multiple clinical and virological endpoints. The primary endpoint was time to resolution of lower respiratory tract disease (LRTD) symptoms to mild severity. Secondary endpoints included time to complete resolution of all 13 RSV-related symptoms, improvement in the Patient Global Impression of Severity (PGI-S) score, viral load reduction, hospitalization rates, and safety outcomes. Patient-reported outcomes were measured through validated symptom scales such as the RiiQ™ 29-parameter symptom scale.
Trial Results
Although the primary endpoint of reducing the time to mild LRTD symptoms was not met, the trial produced robust secondary and subgroup results indicating strong clinical benefit. Overall, patients treated with zelicapavir showed a 2.2-day faster complete resolution of all RSV symptoms compared to placebo, while high-risk subgroup patients experienced a remarkable 6.7-day faster resolution. On the RiiQ™ symptom scale, the general population saw a 3.6-day improvement whereas the high-risk group had a 7.2-day benefit. Hospitalization rates were significantly lower in the treatment group (1.7%) versus placebo (5.0%), reflecting a more than two-thirds relative risk reduction.
Virologically, zelicapavir led to faster viral clearance, with a 4 to 5-day earlier time to undetectable viral load and a higher proportion of patients achieving undetectable virus by end of treatment. The PGI-S score improved significantly, showing a 2-day quicker improvement in symptom severity among patients receiving the drug.
Safety Profile
Zelicapavir demonstrated a favorable safety and tolerability profile consistent with placebo. Adverse events were mainly mild, with the most common side effects being mild diarrhea and asthma exacerbation (in small percentages). No serious adverse events led to treatment discontinuation, highlighting the drug’s excellent safety in this vulnerable population.
Public Health Implications
The positive Phase 2b results represent an important advancement in addressing the unmet need for effective antiviral treatments for RSV in high-risk adults. Such patients often experience prolonged illness and are at heightened risk of hospitalization and severe outcomes from RSV infection. An oral, easily administered antiviral like zelicapavir could reduce symptom burden, prevent complications, lower hospital admissions, and potentially decrease healthcare costs and morbidity associated with RSV in older adults and those with cardiopulmonary conditions.
Key Opinions
Scott T. Rottinghaus, M.D., Chief Medical Officer of Enanta Pharmaceuticals expressed strong optimism about the trial outcomes, noting that zelicapavir is the first antiviral to show significant clinical benefit in high-risk adult outpatients with RSV. He emphasized that the data validate the drug’s mechanism and support advancing into a Phase 3 registrational trial with well-defined endpoints. Mohamed Fayed, M.D., a principal investigator from UCSF Fresno, highlighted the compelling improvements in symptoms and the potential to improve patient outcomes significantly. Enanta’s leadership also stated plans to refine Phase 3 trial design to focus on the high-risk subgroup and relevant patient-reported outcomes for regulatory approval.
References
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, 29 Sept 2025, Enanta Pharmaceuticals, https://ir.enanta.com/news-releases/news-release-details/enanta-pharmaceuticals-reports-positive-topline-results-its
About Respiratory Syncytial Virus, Enanta Pharmaceuticals, https://www.enanta.com/pipeline/respiratory-syncytial-virus/
A Study to Assess EDP-938 for the Treatment of Acute Upper Respiratory Tract Infection with Respiratory Syncytial Virus in Adult Subjects (RSVP), ClinicalTrials.gov ID NCT04196101, https://clinicaltrials.gov/study/NCT04196101