Updates on the Development of an ASO Therapy for Angelman Syndrome

Quick Overview

Becky Crean, Director of Clinical Development at Ionis Pharmaceuticals, provided an update on the development of an antisense oligonucleotide (ASO) therapy for Angelman Syndrome at the 2020 FAST Science Summit. Ionis Pharmaceuticals has been working on developing ASOs for various neurological diseases, including Angelman Syndrome. They have identified a lead compound with a better profile and are completing preclinical studies. If all goes as planned, a clinical trial is expected to start in the second half of 2021. The trial will assess the safety and efficacy of the ASO and will include measures that are important to patients and families. Ionis Pharmaceuticals is committed to bringing the best drug forward for the Angelman community and encourages participation in natural history studies and clinical trials.

Introduction

Becky Crean, Director of Clinical Development at Ionis Pharmaceuticals, expresses gratitude to the FAST Angel community for their time and discusses the importance of developing a treatment for Angelman Syndrome. She provides an update on the advances made in the program since the previous year and introduces the Ionis team members dedicated to the Angelman program.

About Ionis Pharmaceuticals

Ionis Pharmaceuticals was founded in 1989 with the goal of turning antisense oligonucleotides (ASOs) into a therapy. The company has focused on developing and advancing this technology for the past 30 years. Ionis has successfully developed Spinraza for spinal muscular atrophy and Tegsedi for polyneuropathy. They have a pipeline of ASOs in development for various neurological diseases, including Angelman syndrome.

Angelman Syndrome and ASO Therapy

Angelman syndrome is caused by a deletion or mutation of the maternal copy of UBE3A. Ionis’s ASO therapy aims to bind to the long non-coding antisense transcript that silences the paternal copy of UBE3A, thereby increasing UBE3A protein production in the brain. The program started in 2012 and has since undergone extensive screening and preclinical studies.

Current Status of the Program

Ionis announced in December that they planned to initiate a clinical trial with their lead ASO therapy in the second half of 2021. Through ongoing testing, they identified a new lead with a better profile than the original drug. The remaining preclinical studies with this compound are being completed. Ionis and Biogen are working closely together to bring the best drug forward for the Angelman community.

Patient Perspective in Drug Development

Ionis emphasizes the importance of including the patient and family perspective in the drug development process. They collaborate with patient communities to understand the most relevant aspects of the disease and the focus of a new therapy. In the Angelman syndrome trial, Ionis will assess all aspects of the disorder that are important to patients and families. They aim to ease the burden of participating in the trial and incorporate home measures and video techniques to capture meaningful change in the child’s daily life.

Details of the Clinical Trial

The clinical trial is expected to start in the second half of 2021 and will be a global study with sites around the world. The ASO will be administered through a lumbar puncture, and patients will be given anesthesia during the procedure. The trial will assess the safety and tolerability of the drug and measure important aspects such as communication, seizures, cognitive abilities, and sleep difficulties. There will be no placebo in this trial, and each patient will receive several doses of the ASO over a period of time.

Delivering ASOs and Safety

ASOs do not cross the blood-brain barrier, so they need to be delivered into the cerebral spinal fluid through a lumbar puncture. Ionis has extensive experience with this method and has delivered ASOs to over 11,000 patients. Lumbar punctures are common and safe procedures, with potential side effects such as headaches, backaches, nausea, and dizziness. Ionis is confident in the safety profile of their drug and will provide treatment to the broadest population in Angelman syndrome.

How to Prepare for the Future

Crean encourages participation in ongoing natural history studies, staying active in the community, and considering participation in clinical trials. She recommends discussing the pros and cons of each drug and trial with physicians. The Angelman clinical trial website is a valuable resource for learning about the clinical trial process and available drug trials. Crean concludes by expressing Ionis’s commitment to the Angelman community and encourages the audience to stay tuned for future updates.