obudanersen (ION582) / Ionis - LARVOL DELTA

CHAMPION: A Study to Evaluate the Efficacy and Safety of Obudanersen (ION582) in Children and Adults With Angelman Syndrome (AS) (clinicaltrials.gov) - P3 | N=30 | Not yet recruiting | Sponsor: Ionis Pharmaceuticals, Inc.

New P3 trial

HALOS: A Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of Multiple Ascending Doses of ION582 in Participants With Angelman Syndrome (clinicaltrials.gov) - P1/2 | N=71 | Active, not recruiting | Sponsor: Ionis Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • UBE3A

HALOS: A Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of Multiple Ascending Doses of ION582 in Participants With Angelman Syndrome (clinicaltrials.gov) - P1/2 | N=70 | Recruiting | Sponsor: Ionis Pharmaceuticals, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • UBE3A

REVEAL: A Phase 3 Study of ION582 in Angelman Syndrome (clinicaltrials.gov) - P3 | N=26 | Recruiting | Sponsor: Ionis Pharmaceuticals, Inc. | N=14 ➔ 26

Enrollment change • UBE3A

Emerging disease-modifying therapies for Angelman syndrome: A comprehensive review for pediatric neurologists. (PubMed, Brain Dev) - "The molecular pathophysiology of AS, natural history considerations critical for trial interpretation, and the current evidence for antisense oligonucleotide (ASO) therapies (ION582, GTX-102/apazunersen, rugonersen), gene replacement approaches (MVX-220), and next-generation strategies including CRISPR-based gene editing, artificial transcription factors, small molecules, and novel delivery platforms are reviewed. Critical challenges include outcome measurement limitations, genotype stratification, long-term safety monitoring, and ensuring equitable access. These advances herald a transformation in AS clinical care and represent a milestone in precision pediatric neurology."

Journal • Review • Ataxia • CNS Disorders • Developmental Disorders • Epilepsy • Gene Therapies • Genetic Disorders • Mental Retardation • Movement Disorders • Pediatrics • UBE3A

REVEAL: A Phase 3 Study of ION582 in Angelman Syndrome (clinicaltrials.gov) - P3 | N=158 | Recruiting | Sponsor: Ionis Pharmaceuticals, Inc. | N=30 ➔ 158

Enrollment change • UBE3A

ION582-CS2: REVEAL: A Phase 3 Study of ION582 in Angelman Syndrome (clinicaltrialsregister.eu) - P2/3 | N=14 | Not yet recruiting | Sponsor: Ionis Pharmaceuticals Inc.

New P2/3 trial • UBE3A

HALOS: A Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of Multiple Ascending Doses of ION582 in Participants With Angelman Syndrome (clinicaltrials.gov) - P1/2 | N=70 | Recruiting | Sponsor: Ionis Pharmaceuticals, Inc. | Active, not recruiting ➔ Recruiting | N=51 ➔ 70

Enrollment change • Enrollment open • UBE3A

Ionis receives U.S. FDA Breakthrough Therapy designation for ION582 in Angelman syndrome (Businesswire) - "This Breakthrough Therapy designation is based on results from the Phase 1/2 HALOS study..."

Breakthrough therapy • Rare Diseases

REVEAL: A Phase 3 Study of ION582 in Angelman Syndrome (clinicaltrials.gov) - P3 | N=210 | Recruiting | Sponsor: Ionis Pharmaceuticals, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open

REVEAL: A Phase 3 Study of ION582 in Angelman Syndrome (clinicaltrials.gov) - P3 | N=210 | Not yet recruiting | Sponsor: Ionis Pharmaceuticals, Inc.

New P3 trial

Ionis reports fourth quarter and full year 2024 financial results (Businesswire) - "ION582 on track to initiate Phase 3 development in Angelman syndrome (AS) in H1:2025."

New P3 trial • Rare Diseases

HALOS: A Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of Multiple Ascending Doses of ION582 in Participants With Angelman Syndrome (clinicaltrials.gov) - P1/2 | N=51 | Active, not recruiting | Sponsor: Ionis Pharmaceuticals, Inc. | Trial completion date: Jan 2025 ➔ Mar 2029 | Trial primary completion date: Jan 2025 ➔ Mar 2029

Trial completion date • Trial primary completion date • UBE3A

HALOS: A Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of Multiple Ascending Doses of ION582 in Participants With Angelman Syndrome (clinicaltrials.gov) - P1/2 | N=51 | Active, not recruiting | Sponsor: Ionis Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • UBE3A

This study is meant to evaluate the effects of a drug product called ION582 in patients with Angelman syndrome (genetic disorder that mainly affects the nervous system). This study will evaluate the safety, how the organism tolerates the drug product, how the product is metabolized by the organism and what are the effects of the product on the body. (clinicaltrialsregister.eu) - P1/2 | N=55 | Sponsor: Ionis Pharmaceuticals, Inc.

New P1/2 trial • Ataxia • CNS Disorders • Developmental Disorders • Epilepsy • Genetic Disorders • Mental Retardation • Movement Disorders • Psychiatry • Targeted Protein Degradation • UBE3A

HALOS: A Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of Multiple Ascending Doses of ION582 in Participants With Angelman Syndrome (clinicaltrials.gov) - P1/2 | N=44 | Recruiting | Sponsor: Ionis Pharmaceuticals, Inc. | Trial completion date: Dec 2023 ➔ Jan 2025 | Trial primary completion date: Jul 2023 ➔ Jan 2025

Trial completion date • Trial primary completion date • UBE3A