Roche Pharma Research and Early Development

Quick Overview

Roche Pharma Research and Early Development presented at the 2018 FAST Science Summit, discussing their progress in developing a therapy for Angelman syndrome. They shared data on their RNA therapy, which targets the loss of UBE3A in the brain, and their efforts to increase UBE3A protein levels. They also presented a disease concept model, developed in collaboration with the Angelman community, which identified key concepts for measuring efficacy in clinical trials, such as expressive communication, independence, and reduction of maladaptive behaviors. Roche also announced plans for an endpoint enabling study, focused on developing new endpoints for future clinical trials. They emphasized the importance of collaboration and the need for a collaborative approach in advancing therapy development for Angelman syndrome.


In this talk, we will be discussing the work being done by Roche Pharma Research and Early Development in the field of Angelman syndrome. We will provide an overview of their discovery program, highlight their collaboration with the AS community, and discuss their plans for endpoint development.

Meghan Miller’s Background

Meghan Miller is a Ph.D. in biomedical sciences from the Department of Pharmacology at the University of California, San Diego. She joined Roche in 2012 as a postdoc in the neuroscience group, focusing on stem cell biology and genetic neurodevelopmental disorders. In 2015, she became a discovery project leader in the rare disease group, specifically working on Angelman syndrome.

Michelle Krishnan’s Background

Michelle Krishnan is a pediatrician and translational medicine leader at the rare disease unit at Roche. She specializes in disorders affecting the developing brain and has a background in neuroscience. She is also involved in clinical development for rare disease disorders.

Overview of Roche’s Discovery Program

Roche’s rare disease group is dedicated to developing breakthrough treatments for individuals with life-threatening or life-limiting rare diseases. Their approach is rooted in three pillars: science, understanding the disease, and collaboration with the community.

Their scientific approach involves targeting RNA, specifically using antisense oligonucleotides to modulate gene expression or activity. This approach has shown promise in other diseases such as spinal muscular atrophy.

In Angelman syndrome, the loss of UBE3A in the brain is due to a genetic defect. Roche’s therapy aims to target the endogenous RNA that silences the paternal UBE3A copy, allowing for the expression of the normal copy and replacing the missing UBE3A protein.

The Concept Model

Roche has collaborated with the AS community, particularly ABOM, to develop a concept model. This model aims to define the burden of the disease and identify meaningful measures for assessing efficacy in drug studies.

The model was developed through a literature review and interviews with expert clinicians and caregivers. The key concepts identified were expressive communication, independence, self-care, sleep improvement, reduction of maladaptive behaviors, and motor skills improvement.

These concepts will guide the development of endpoints for future clinical trials and help communicate with health authorities about the regulatory path for Angelman syndrome therapies.

Endpoint Development

Roche is planning an endpoint enabling study to develop new endpoints for Angelman clinical trials. The study will focus on the home environment and use new digital approaches, such as wearable devices, to gather accurate and realistic data.

The study will involve 40 children and 10 adults with Angelman syndrome, as well as 20 typically developing controls for comparison. The goal is to develop quantitative measures that accurately reflect the impact of therapies on daily living needs.

The data collected in this study may also be used as a control cohort for future trials, potentially reducing the need for placebo groups or shortening the placebo period.


Roche Pharma Research and Early Development is dedicated to developing transformative therapies for individuals with Angelman syndrome. Their scientific approach, collaboration with the community, and focus on endpoint development are all aimed at bringing effective treatments to the market.

The work being done by Roche, along with the contributions of caregivers and individuals with Angelman syndrome, is paving the way for future clinical trials and the potential for life-changing therapies.

Talk details

  • Title: Roche Pharma Research and Early Development
  • Author(s): Meghan Miller, Michelle Krishnan
  • Author(s)’ affiliation: Roche Pharmaceuticals
  • Publication date: 2019-01-10
  • Collection: 2018 FAST Science Summit