Enanta Pharmaceuticals advances zelicapavir into late-stage RSV development with FDA-backed Phase 2b/3 trials in adults and pediatrics, aiming to deliver topline data in 2027.
Written By: Sana Khan, BPharm
Reviewed By: Pharmacally Editorial Team
Enanta Pharmaceuticals has secured a late-stage development pathway for zelicapavir after a successful End-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA). The company plans to initiate a global registrational Phase 2b/3 study in adults at high risk of severe RSV outcomes in the fourth quarter of 2026, with topline Phase 2b data expected in 2027.
Enanta will also begin a Phase 2b trial in pediatric RSV patients during the third quarter of 2026, with topline results anticipated in 2027.
Scientific and Clinical Context
RSV remains a major cause of respiratory illness worldwide, particularly among infants, older adults, and immunocompromised individuals. Despite preventive advances, no antiviral therapy has yet been approved for RSV.
Zelicapavir is an investigational oral antiviral that targets the RSV nucleoprotein (N-protein). Zelicapavir’s N-protein inhibition represents a novel antiviral approach distinct from RSV fusion inhibitors and has demonstrated a high barrier to resistance in preclinical studies. By inhibiting viral replication rather than viral entry, the drug has shown activity against both RSV-A and RSV-B strains.
The FDA has granted zelicapavir Fast Track designation, reflecting the significant unmet need for effective RSV therapies.
Registrational Adult Trial Details
The upcoming Phase 2b/3 study will enroll adult outpatients who test positive for RSV and have experienced respiratory symptoms for three days or less. Eligible participants must have at least one major risk factor for severe disease, including age 75 years or older, chronic obstructive pulmonary disease (COPD), or congestive heart failure (CHF).
Participants will receive oral zelicapavir 800 mg or placebo once daily for seven days and will be followed for 28 days. The primary endpoint is time to complete resolution of all 13 RSV symptoms measured using the RiiQ™ symptom assessment tool. Key secondary endpoints include RSV-related hospitalization, additional clinical efficacy measures, antiviral activity, and safety outcomes.
The Phase 2b portion will enroll at least 200 patients to confirm treatment effect size before expansion into the Phase 3 portion, which is expected to include approximately 660 patients.
The trial builds on findings from the Phase 2 RSVHR Trial (NCT05568706), where patients with COPD, CHF, or age 75 years or older experienced a 6.7-day improvement in symptom resolution versus placebo. RSV-related hospitalization occurred in 5% of placebo-treated patients compared with 0% of zelicapavir-treated patients.
Pediatric Development Program
The pediatric Phase 2b study will evaluate approximately 150 hospitalized and non-hospitalized children aged 28 days to 36 months who test positive for RSV within 72 hours of symptom onset. Patients will receive age-adjusted zelicapavir dosing or placebo once daily for seven days.
The primary endpoint is time to complete resolution of RSV clinical signs using Enanta’s proprietary RESOLVE-P scoring tool. Secondary endpoints include additional efficacy measures, antiviral activity, and safety assessments. The study will be conducted in Thailand through collaborations with the Penta Foundation and the AMS-PHPT Research Unit at Chiang Mai University.
A prior pediatric Phase 2 study demonstrated antiviral activity and faster symptom resolution in children aged 28 days to 3 years, providing the foundation for the upcoming Phase 2b trial.
Clinical Implications
Following its End-of-Phase 2 meeting, Enanta aligned with the FDA on a streamlined registrational pathway through a single Phase 2b/3 study. Company leadership highlighted the opportunity to generate confirmatory datasets in both adult and pediatric populations during 2027, strengthening the evidence package for future regulatory submissions.
Path Forward
Enrollment for the pediatric Phase 2b study is expected to begin in the third quarter of 2026, followed by initiation of the adult registrational trial in the fourth quarter. Both programs are expected to deliver topline data in 2027.
If successful, zelicapavir could become the first oral antiviral for RSV, complementing vaccines and monoclonal antibodies while addressing a significant unmet treatment need across pediatric and high-risk adult populations.
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About the Writer
Sana Jamil Khan (LinkedIn) is a B. Pharm graduate with a strong interest in medical writing and scientific communication. Her work focuses on interpreting clinical research, exploring developments in pharmaceutical science, and presenting complex medical information in a clear and accessible manner. She is particularly interested in topics related to human clinical studies, drug safety observations, and emerging therapeutic research.