An Update on HALOS Clinical Trial in Individuals Living with Angelman Syndrome
Dr. Becky Crean, Executive Director of Clinical Development at Ionis Pharmaceuticals, provided an update on the HALOS clinical trial for individuals living with Angelman Syndrome. The trial, which is in its early Phase 1/2 stage, aims to determine the safety and tolerability of the compound ION582 in patients with Angelman Syndrome. Preliminary findings from the trial show that ION582 has been well tolerated at all dose levels tested so far, with no concerning safety trends observed. Early signs of clinical improvement, such as changes in EEG activity and clinical measures, have also been observed. The trial has completed enrollment, and data analysis is ongoing. The next steps include completing the data accrual and analyzing the data from the trial, as well as continuing the long-term dosing in the second part of the trial. The ultimate goal is to develop a treatment that can benefit all individuals with Angelman Syndrome.
Dr. Becky Crean, Executive Director of Clinical Development at Ionis Pharmaceuticals, provided an update on the HALOS clinical trial during the 2023 FAST Science Summit. The HALOS trial is focused on developing a treatment for Angelman syndrome using a compound called ION582. Dr. Crean discussed the approach to the trial, preliminary findings, and the next steps in the research.
Approach to Developing a Treatment
The HALOS trial is an early Phase 1/2 trial designed to answer the question of whether ION582 is safe and tolerable in patients with Angelman syndrome. The trial consists of two parts: the Multiple Ascending Dose (MAD) portion and the long-term extension. The MAD portion looks at different dose levels and dosing intervals in different age groups to assess safety and tolerability. The long-term extension provides additional data on safety and starts to evaluate the clinical impact of the compound.
ION582 is a two prime mo antisense oligonucleotide (ASO) designed to stop the silencing mechanism on the paternal UBE3A gene in the brain. This allows the gene to produce UBE3A protein, which is important for correcting Angelman syndrome. The compound was chosen based on its safety and tolerability observed in animal studies. It is a two prime mo ASO, which has greater potency for reducing the target RNA and greater tolerability in CNS disorders.
Dr. Crean shared some preliminary findings from the HALOS trial. The compound has been well tolerated at all dose levels tested so far, with no concerning safety trends observed. Adverse events reported during the trial have been consistent with the symptoms associated with Angelman syndrome. Laboratory assessments have shown no safety signals. EEG data has indicated a reduction in delta activity and an increase in theta activity, suggesting improvements in brain activity. Clinical measures, such as the Clinical Global Impression of Change (CGI) and the Bayley assessment, have shown some level of improvement in a majority of patients.
The primary goal moving forward is to complete the data accrual in the HALOS trial and analyze the data from the MAD portion. The final data cut and readout are expected to occur around mid-2024. Participants will continue in the trial’s long-term extension phase to provide additional data on safety and clinical benefits. Collaboration with other industry sponsors and analysis of natural history study data will also continue.
Acknowledgements and Questions
Dr. Crean expressed gratitude to the HALOS participants and study sites for their commitment and partnership. She also addressed questions from the audience, including the consideration of age and genotype in data analysis and the inclusion of new territories in future trials.
In conclusion, the HALOS trial has made significant progress, and the preliminary findings are encouraging. The focus now is on completing the trial, analyzing the data, and planning for future stages of development.
- Title: An Update on HALOS Clinical Trial in Individuals Living with Angelman Syndrome
- Author(s): Rebecca Crean
- Author(s)’ affiliation: Ionis Pharmaceuticals
- Publication date: 2023-11-12
- Collection: 2023 FAST Science Summit