Ionis' antisense therapy shows promise in Angelman syndrome

Ionis Pharmaceuticals has recently released promising data from a phase 1/2 trial of its experimental antisense therapy for Angelman syndrome (AS), a rare neurodevelopmental disorder. With plans to advance to late-stage development next year, Ionis aims to address this condition that impacts approximately one in every 21,000 people worldwide.

Angelman syndrome is a genetic disorder resulting from a loss of function in the maternal UBE3A gene. It manifests in early childhood with severe developmental delays in motor skills, language, cognitive abilities, as well as seizures and coordination issues. The investigational therapy by Ionis, known as ION582, aims to unsilence the normal paternal UBE3A gene, thereby increasing the production of the UBE3A protein in the brain. The US Food and Drug Administration has already granted ION582 orphan drug and rare pediatric designations.

The HALOS trial, an open-label study, has been assessing three different doses of ION582 in 51 patients aged between two and 50 years across six countries. Findings from the three-month multiple-ascending dose segment of the trial indicated significant clinical improvements in several functional domains, such as communication, cognition, and motor functions. According to the company, 97% of patients in the medium and high dose groups demonstrated symptom improvement based on the Symptoms of Angelman Syndrome-Clinician Global Impression-Change scale. Furthermore, ION582 exhibited a favorable safety and tolerability profile across all dose levels.

Lynne Bird, a HALOS study investigator from UC San Diego, remarked on the encouraging results, noting that AS is a serious disorder with life-long impairments that currently only has supportive care options. The promising data from ION582 shows consistent improvements beyond what is typically observed in the natural progression of the disease.

Brett Monia, the CEO of Ionis, expressed the company’s enthusiasm about the trial results. He emphasized Ionis' commitment to partnering with investigators, regulators, and the AS community to begin phase 3 development of ION582 in the first half of 2025.

This announcement comes shortly after Ionis reported positive results from a late-stage study of another of its investigational therapies, olezarsen. This RNA-targeted antisense medicine is being developed for familial chylomicronaemia syndrome, a rare genetic condition affecting up to 13 people per million in the United States.