An Update on HALOS Clinical Trial in Individuals with Angelman Syndrome
Dr. Rebecca Crean, Executive Director of Clinical Development at Ionis Pharmaceuticals, provided an update on the HALOS clinical trial for individuals with Angelman syndrome. The trial is testing an antisense oligonucleotide (ASO) called ION582, which is designed to stop the silencing mechanism on the paternal UBE3A gene and produce the UBE3A protein in the brain. The trial is currently in the Phase 1/2 stage, focusing on safety and tolerability, and has been well-tolerated so far. The trial also includes a long-term extension phase to assess the effects of longer-term dosing. The goal is to gather data from the trial to determine the optimal dose and dosing regimen for the next phase of development. The study is ongoing and involves multiple sites across nine countries. Dr. Crean expressed gratitude to the Angelman community for their involvement and contributions to the research.
In this talk, Dr. Rebecca Crean, Executive Director of Clinical Development at Ionis Pharmaceuticals, provides an update on the HALOS clinical trial for individuals with Angelman syndrome. She discusses the development of the antisense oligonucleotide (ASO) compound ION582 and its potential to treat Angelman syndrome. Dr. Crean also highlights the importance of the HALOS trial in assessing the safety and tolerability of the compound.
Ionis Pharmaceuticals and ASO Development
Ionis Pharmaceuticals has been at the forefront of ASO development for many years. The company focuses solely on developing ASOs and has dedicated scientists and researchers working on various disorders and medical conditions. With their experience in ASO development, Ionis is now working on developing ION582 for Angelman syndrome.
Understanding ION582 and its Mechanism of Action
ION582 is an ASO designed to stop the silencing mechanism on the paternal UBE3A gene, which is associated with Angelman syndrome. It is a 2’-MOE ASO that activates the RNase H cleaving mechanism. The compound has undergone extensive testing in cells, animal models, and nonhuman primates to ensure safety and efficacy.
The HALOS Clinical Trial
The HALOS trial is the first human trial for ION582. It aims to assess the safety and tolerability of the compound in individuals with Angelman syndrome. The trial includes a small group of participants ranging from toddlers to adults with deletion and mutation genotypes. Different dose levels and intervals of the compound are being tested, and all participants receive the active drug.
Trial Design and Measures
The HALOS trial is a Phase 1/2 trial, focusing primarily on safety and tolerability. However, it also aims to gather data on various areas of functioning, such as language, motor skills, learning, seizures, and sleep. Participants undergo tests and assessments both in the clinic and at home to better understand the effects of the compound in different settings.
Progress and Future Plans
The HALOS trial has been progressing well, with all tested dose levels of ION582 being well tolerated and no drug-related adverse events identified. The trial also includes a long-term extension, allowing participants to continue treatment for an additional 12 months. This extension will provide further insights into the compound’s safety, tolerability, and potential clinical benefits.
As the HALOS trial continues, Ionis Pharmaceuticals plans to analyze the CSF (cerebrospinal fluid) levels of UBE3A in their industry-sponsored natural history studies. This analysis will help understand the natural variation in UBE3A levels and how they may change over time. The data generated from the HALOS trial and natural history studies will inform the next phase of development, including expanding the trial to newborns and different genotypes.
Dr. Rebecca Crean expresses gratitude to the Angelman community for their involvement and contributions to the research. She acknowledges the long process of drug discovery and emphasizes the importance of thoroughness and thoughtfulness in early studies. Ionis Pharmaceuticals remains committed to developing effective treatments for Angelman syndrome and aims to use the data from the HALOS trial to advance the program and improve the lives of individuals with Angelman syndrome.
- Title: An Update on HALOS Clinical Trial in Individuals with Angelman Syndrome
- Author(s): Rebecca Crean
- Author(s)’ affiliation: Ionis Pharmaceuticals
- Publication date: 2022-12-03
- Collection: 2022 FAST Science Summit