CARLSBAD, Calif., July 6, 2026
Ionis Pharmaceuticals announced the completion of enrollment for the pivotal pediatric cohort of its global Phase 3 REVEAL study evaluating obudanersen (ION582), an investigational RNA-targeted therapy for Angelman syndrome (AS). The pivotal cohort enrolled 136 participants between 2 and under 18 years of age with genetically confirmed Angelman syndrome caused by UBE3A deletion or UBE3A mutation. The company expects enrollment of the adult cohort to conclude during the third quarter of 2026, while topline data from the Phase 3 study are anticipated in the second half of 2027.
Phase 3 REVEAL Study Evaluates Disease-Modifying RNA Therapy
The REVEAL (NCT06914609) study is a global, randomized, double-blind, controlled Phase 3 clinical trial designed to enroll approximately 158 participants with Angelman syndrome across two patient cohorts. The pediatric cohort serves as the pivotal population for evaluating the study’s primary and secondary efficacy endpoints, while the adult cohort will include participants aged 18 to 50 years. The primary endpoint measures improvements in expressive communication using the clinician-administered Bayley Scales for Infant and Toddler Development-4 (Bayley-4), reflecting one of the most meaningful functional outcomes identified by caregivers. Secondary endpoints evaluate cognition, overall disease severity, communication abilities, motor function, sleep quality, and daily living skills.
Obudanersen Targets the Genetic Cause of Angelman Syndrome
Obudanersen is an investigational antisense RNA-targeted therapy designed to inhibit the UBE3A antisense transcript (UBE3A-ATS), thereby restoring production of the UBE3A protein, which is deficient in individuals with Angelman syndrome. The therapy aims to address the underlying genetic cause of the disorder rather than simply managing symptoms. Angelman syndrome is a rare neurodevelopmental disorder affecting approximately one in 21,000 people worldwide and is characterized by severe intellectual disability, profound communication impairment, motor dysfunction, balance problems, seizures, and lifelong dependence on caregivers. Currently, no approved disease-modifying therapies are available for the condition.
Advertisement
Ionis Expands Late-Stage Development Program in Angelman Syndrome
Building on the progress of the REVEAL study, Ionis plans to initiate the Phase 3 CHAMPION study before the end of 2026 to evaluate obudanersen in individuals with Angelman syndrome caused by uniparental disomy (UPD) or imprinting defect (ID) genotypes. Obudanersen has received U.S. FDA Orphan Drug Designation, Fast Track Designation, and Rare Pediatric Disease Designation, in addition to European Medicines Agency Orphan Drug Designation, highlighting its potential to address a significant unmet need in this rare neurological disorder. The program further strengthens Ionis’ expanding neurology pipeline, which focuses on developing RNA-targeted therapies for rare and serious neurological diseases with limited or no available disease-modifying treatment options.
Source: Ionis Pharmaceuticals press release
