Ionis Pharmaceuticals has reported promising results for its investigational treatment for Angelman syndrome, ION582, which displayed a favorable safety profile and reduced symptoms in patients from the HALOS clinical trial. Data from the six-month follow-up of the Phase 1/2 study indicated that 97% of patients receiving medium and high doses of ION582 showed meaningful improvements in their symptoms, according to the Symptoms of Angelman Syndrome-Clinician Global Impression of Change (SAS-CGI-C) scale.
The trial involved direct spinal injections of ION582 at low, medium, and high doses over three months. Enhancements were noted in communication, cognition, and motor skills, and the therapy was well tolerated across all dosage levels.
Ionis is planning to initiate a pivotal Phase 3 study for ION582 in Angelman patients in the first half of 2025 and will refine the trial design in discussions with regulators later this year. Brett Monia, CEO of Ionis, expressed enthusiasm for collaborating with investigators and the Angelman community to advance the development of ION582, highlighting the trial results as a significant advancement in their neurological treatments.
Angelman syndrome arises from mutations in the maternal UBE3A gene, which inhibits production of the UBE3A protein. The treatment ION582 is designed to activate the paternal UBE3A gene by blocking a silencing molecule.
The HALOS clinical trial enrolled 51 participants aged 2 to 50 years. Following the first phase, eligible patients will move to the second phase, which will monitor the effects of medium and high doses of ION582 for an additional 12 months, with a third part extending follow-up for another four years.
Key efficacy measures included an assessment of changes in communication, cognition, motor function, sleep, seizures, and daily living skills. Parent-reported evaluations revealed that 72% of patients improved in fine motor skills, 67% in cognition, and 69% in expressive communication. Improvements in nonverbal communication were seen in 60% of patients, while receptive communication skills improved in 89% and expressive communication in 84%.
The study also indicated improvements in socialization skills for 63% to 87% of participants, daily living skills for 74% to 82%, fine motor skills for 63%, and gross motor skills for 53%. Overall cognition improvements were reported in 85% of patients, with sleep and behavior also showing positive changes.
Dr. Lynne Bird, a clinical pediatrics professor and investigator on the HALOS study, emphasized the significance of ION582’s promising data as a potential breakthrough in treating a disorder that currently has no curative options. Results from the trial were presented at the 2024 Angelman Syndrome Foundation Family Conference in Sandusky, Ohio. ION582 has also received orphan drug and rare pediatric disease designations from the U.S. Food and Drug Administration (FDA) to facilitate its development.