An open label phase 1/2 trial of Ionis’s antisense oligonucleotide therapy in 51 patients with the rare genetic condition Angelman syndrome resulted in 97% of those given a medium or high dose of the therapy achieving significant symptom improvement measured by a clinical score known as the Symptoms of Angelman Syndrome–Clinician Global Impression-Change.
The study included people aged 2 to 50 years and was carried out across 11 sites in 6 countries. The first part evaluated three doses of the therapy for three months and then included a final assessment at 6 months. Most patients have transitioned into a long-term extension part of the study testing the two higher doses for an additional 12 months. The company also plans a third part of the study where eligible participants will continue to be monitored for up to 4 years.
Using another clinical score, Bayley-4, the researchers also saw 67% or higher improvements in communication, 67% improvement in cognition and improvements in gross and fine motor function that ranged between 46–72%. Importantly, safety and tolerability of the therapy were good at all dose levels.
Two parent reported scores, Vineland-3 and Observer-Reported Communication Ability, for children with Angelman also improved after treatment with Ionis’s candidate therapy ION582.
"Angelman syndrome is a serious neurodevelopmental disorder with life-long impairments and dependence on caregivers, for which we currently have only supportive care," said Lynne Bird, professor of clinical pediatrics at University of California San Diego and the senior study investigator for Ionis, in a press statement.
"We are very encouraged by these promising data with ION582, showing consistent improvements over what we observe in the natural course of the disease."
Filling an unmet need
Ionis specializes in antisense oligonucleotide therapies (ASOs) that target messenger RNA and change gene expression to correct disease-causing mutations such as the one that causes Angelman syndrome.
Ionis began life as Isis Pharmaceuticals and was one of the first companies to start developing ASO therapies in the 90’s. The company changed its name to Ionis in 2015 and now has a number of approved ASOs on the market, such as Spinraza (nusinersen) for treatment of spinal muscular atrophy, and also has many in development.
ASO’s lend themselves to treatment of rare genetic diseases and have brought hope to many families and patients with no other treatment options. Angelman is one such condition. Thought to affect around 1 in 20,000 births, it is caused by a mutation causing a lack of function of part of chromosome 15. In most cases the mutation is spontaneous and not inherited.
The condition causes neurological symptoms that impact intellectual development and movement ability and there is currently no cure or specific treatments available other than physical therapy or treatment for some of the symptoms such as epilepsy medication for patients with seizures.
Based on the positive results of this trial, Ionis now plans to move the therapy to phase 3 at the beginning of 2025.