Ionis Pharmaceuticals has completed enrollment in the pivotal cohort (Cohort 1) of the global phase 3 REVEAL study evaluating obudanersen (ION582), an investigational RNA-targeted medicine for people living with Angelman Syndrome (AS), a serious and rare neurodevelopmental disorder associated with significant impairments in communication, physical function and cognition. The pivotal cohort enrolled 136 participants aged 2 to < 18 years old with a confirmed clinical diagnosis of AS with genetic confirmation of either a UBE3A deletion or UBE3A mutation. The adult cohort (Cohort 2) comprised participants aged 18 to ≤ 50 years old living with AS is expected to complete enrollment in the third quarter of 2026. Topline data from the REVEAL study is expected in the second half of 2027.

Holly Kordasiewicz, PhD, Executive Vice President (EVP), Chief Development Officer (CDO), Ionis, said, "Completion of enrollment in the pivotal cohort of REVEAL marks an important step towards a potential disease modifying treatment for people living with this serious and complex neurological condition, for which there are no approved medicines. Guided by input from the Angelman community, REVEAL was intentionally designed to evaluate obudanersen across a broad range of people living with Angelman syndrome, reflecting the real-world diversity of this condition. We are deeply grateful to the entire Angelman syndrome community, especially the participants and their families, whose partnership made this achievement possible.”

REVEAL (NCT06914609) is a global, randomised, double-blind, controlled phase 3 study that will enroll approximately 158 individuals with a confirmed clinical diagnosis of AS with genetic confirmation of either a UBE3A deletion or UBE3A mutation. REVEAL is comprised of two cohorts. Cohort 1 (pivotal cohort) includes pediatric participants aged 2 to < 18 years old and serves as the population for evaluation of primary and secondary endpoints. Cohort 2 (adult cohort) will include adult participants aged 18 to ≤ 50 years old. The primary endpoint is improvement in expressive communication as assessed by the Bayley Scales for Infant and Toddler Development-4 (Bayley-4), an objective and direct clinician-administered assessment of clinical functioning. Deficits in expressive communication are reported to be the symptoms most meaningful to caregivers of people with AS. Secondary endpoints include overall disease severity, cognition, communication, sleep, motor functioning and daily living skills, in addition to other exploratory endpoints.

Ionis also plans to advance obudanersen into the phase 3 CHAMPION study to evaluate obudanersen in people with AS who have uniparental disomy (UPD) or Imprinting Defect (ID) genotypes. The CHAMPION study is on track to initiate before the end of 2026.