Ionis Completes Enrollment in Pivotal Cohort of Phase 3 REVEAL Study for Obudanersen in Angelman Syndrome
核心洞察
Ionis Pharmaceuticals (搜索) completed enrollment of 136 pediatric participants in the pivotal cohort of the Phase 3 REVEAL study evaluating obudanersen (搜索) for Angelman syndrome (搜索).
The global, randomized, double-blind, controlled trial will assess improvement in expressive communication as its primary endpoint using the Bayley-4 assessment.
Topline data from the REVEAL study is anticipated in the second half of 2027, with the adult cohort expected to complete enrollment in Q3 2026.
Ionis Pharmaceuticals (搜索), Inc. announced today that it has completed enrollment in the pivotal cohort (Cohort 1) of the global Phase 3 REVEAL study evaluating obudanersen (搜索) (ION582), an investigational RNA-targeted antisense medicine for Angelman syndrome (搜索) (AS). The pivotal cohort enrolled 136 participants aged 2 to less than 18 years old with a confirmed clinical diagnosis of AS and genetic confirmation of either a UBE3A (搜索) deletion or UBE3A mutation.
"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," said Holly Kordasiewicz, Ph.D., executive vice president and chief development officer at Ionis. "Guided by input from the Angelman community, REVEAL was intentionally designed to evaluate obudanersen (搜索) across a broad range of people living with Angelman syndrome (搜索), reflecting the real-world diversity of this condition."
Study Design and Endpoints
REVEAL (NCT06914609) is a global, randomized, double-blind, controlled Phase 3 study that will enroll approximately 158 individuals with a confirmed clinical diagnosis of AS. The study comprises two cohorts: Cohort 1, the pivotal cohort, includes pediatric participants aged 2 to less than 18 years old and serves as the population for evaluation of primary and secondary endpoints. Cohort 2, the adult cohort, will include participants aged 18 to 50 years old and is expected to complete enrollment in the third quarter of 2026.
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.
Mechanism of Action and Regulatory Designations
Obudanersen (搜索) is designed to inhibit the expression of the UBE3A (搜索) antisense transcript (UBE3A-ATS) and increase production of UBE3A protein. The U.S. Food and Drug Administration and European Medicines Agency have granted Orphan Drug designation to obudanersen for the treatment of AS. Additionally, the FDA granted Fast Track and Rare Pediatric designations to the investigational therapy.
Angelman Syndrome (搜索) Disease Burden
Angelman syndrome (搜索) is a rare, genetic neurological disease affecting an estimated 1 in 21,000 people worldwide, caused by the loss of function of the maternal UBE3A (搜索) gene. The condition typically presents in infancy and is characterized by profound intellectual disability, balance issues, motor impairment, and debilitating seizures. Most people with AS are unable to speak. While individuals with AS have a normal lifespan, they require complete care from a caregiver. Some symptoms can be managed with existing medicines; however, there are no approved disease-modifying therapies.
Next Steps and the CHAMPION Study
Topline data from the REVEAL study is expected in the second half of 2027. Ionis also plans to advance obudanersen (搜索) into a second Phase 3 study, CHAMPION, which will evaluate the therapy 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.
Ionis has an established track record in neurological disease medicines, including SPINRAZA (nusinersen), the first approved treatment for spinal muscular atrophy; WAINUA (eplontersen) for hereditary transthyretin-mediated amyloid polyneuropathy; and QALSODY (tofersen) for SOD1-ALS. The company's clinical-stage neurology portfolio includes 13 investigational medicines, of which six are wholly owned by Ionis.