Ionis Pharmaceuticals has shared positive results from a phase 1/2 trial of its investigational antisense therapy in patients with the rare neurodevelopmental disorder Angelman syndrome (AS) and has outlined plans to begin late-stage development of the candidate next year.
Affecting an estimated one in every 21,000 people globally, AS is a genetic condition caused by a loss of function in the maternal UBE3A gene. It presents in early childhood as severe developmental delays in motor, language and cognitive functioning, as well as seizures and ataxia.
Ionis’ ION582, which has already been granted orphan drug and rare paediatric designations by the US Food and Drug Administration, is designed to unsilence the normal paternal UBE3A gene to increase production of the UBE3A protein in the brain.
The open-label HALOS trial has been evaluating three doses of the candidate in 51 patients aged two to 50 years across six countries.
Results from the three-month multiple-ascending dose portion of the study demonstrated “consistent and encouraging” clinical improvement on measures assessing all functional domains, including communication, cognition and motor function, the company said.
Overall, 97% of patients in the medium and high dose groups saw an improvement in AS symptoms, as measured by the Symptoms of Angelman Syndrome-Clinician Global Impression-Change scale, and the drug also showed favourable safety and tolerability at all dose levels.
Commenting on the readout, HALOS study investigator Lynne Bird, UC San Diego, said: “AS is a serious neurodevelopmental disorder with life-long impairments and dependence on caregivers, for which we currently have only supportive care.
“We are very encouraged by this promising data with ION582, showing consistent improvements over what we observe in the natural course of the disease.”
Brett Monia, chief executive officer of Ionis, added that the company “looks forward to collaborating with investigators, regulators and members of the AS community to initiate phase 3 development for ION582 in the first half of 2025”.
The results come three months after Ionis shared positive results from a late-stage study of its RNA-targeted investigational ligand-conjugated antisense medicine olezarsen in adults with familial chylomicronaemia syndrome, a rare genetic disease estimated to affect up to 13 people per million in the US.