Roche Angelman Syndrome Program Update

Quick Overview

Dr. Brenda Vincenzi, Global Development Leader and Senior Medical Director at Roche Pharmaceuticals, provided an update on the Roche Angelman Syndrome program at the 2022 FAST Science Summit. She discussed the progress of Rugonersen, an antisense oligonucleotide, in drug development and provided an update on the TANGELO Phase 1 study and the PET imaging study. Dr. Vincenzi also announced that Roche will be adding Alogabat, a new investigational drug for individuals with the deletion genotype of Angelman Syndrome, to their pipeline. She emphasized the importance of staying objective and not sharing data or observations from ongoing clinical trials, as it can influence the outcome. Dr. Vincenzi highlighted the scientific rationale for studying Alogabat in deletion genotypes and explained how the drug enhances the function of GABA-R alpha-5 receptors. The Aldebaran Phase 2a study for Alogabat is set to begin in the first half of next year.

Introduction

Dr. Brenda Vincenzi, Global Development Leader and Senior Medical Director at Roche Pharmaceuticals, provided an update on the Roche Angelman Syndrome program at the 2022 FAST Science Summit. In her presentation, she discussed the progress of Rugonersen, an antisense oligonucleotide, LNA, in drug development, as well as updates on the TANGELO Phase 1 drug study and the PET imaging study. Dr. Vincenzi also announced the addition of Alogabat, a new drug for individuals with the deletion genotype of Angelman Syndrome, to Roche’s pipeline.

Overview of the Angelman Syndrome Program

Roche has been working with the Angelman Syndrome community for almost eight years. They developed a disease concept model in collaboration with ABOM and conducted an observational study called FREESIAS in partnership with Biogen and Ionis. The FREESIAS study was completed last year, and a publication is forthcoming. In 2020, Roche initiated the TANGELO Phase 1 drug study with Rugonersen, which has completed its first part and is now in the second part. Additionally, Roche started the PET imaging study last year, which has been completed.

Rugonersen: Drug Development and Updates

Rugonersen is an antisense oligonucleotide that targets the UBE3A protein, which is deficient in individuals with Angelman Syndrome. Dr. Vincenzi explained that Rugonersen aims to have a broad label, addressing Angelman Syndrome as a whole, including all ages and genotypes. The TANGELO study is currently enrolling participants aged 1 to 12 with mutation and deletion genotypes. The study’s objective is to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of Rugonersen. Dr. Vincenzi emphasized the importance of staying objective and not sharing data or observations from the ongoing study, as it could influence the study’s outcome.

PET Imaging Study

The PET study is an imaging study that aims to understand the biodistribution of Rugonersen in the body. Healthy adult volunteers were administered a radiolabeled form of Rugonersen, and PET scans were performed to track the drug’s movement. The study has been completed, with 20 volunteers enrolled and 152 full-body PET scans conducted. Data analysis is currently underway, and the results will be shared with the community in due time.

Introduction of Alogabat

Roche has decided to add Alogabat to its pipeline for individuals with the deletion genotype of Angelman Syndrome. Alogabat is a tablet that enhances the function of GABA-R alpha-5 receptors, which are important for brain development and neuronal function. The drug has shown an acceptable safety and tolerability profile in previous studies. Roche will be conducting the Aldebaran Phase 2a study to investigate the pharmacokinetics, safety, tolerability, and mechanism of action of Alogabat in individuals with the deletion genotype. The study will enroll up to 56 participants and is expected to start in the first half of next year.

Conclusion

Dr. Vincenzi concluded her presentation by emphasizing the importance of staying objective and not sharing data or observations from ongoing clinical trials. She assured the community that Roche is committed to transparency and will share data as soon as possible. She also expressed gratitude to the patient council representatives who were involved in reviewing the protocol for the Alogabat trial. The Roche Angelman Syndrome program continues to make progress in developing potential treatments for this rare genetic disorder.