Angelman Biomarker and Outcome Measure Consortium

In partnership with FAST and the Angelman Syndrome Foundation, the A-BOM Consortium is a pre-competitive effort co-directed by Dr. Allyson Berent, FAST’s Chief Science Officer, and Jennifer Panagoulias, RAC, FAST’s head of Regulatory and Policy. The A-BOM is made up of a steering committee with participation from patient advocacy groups, industry, academics, clinicians, and caregivers. The A-BOM steering committee meets quarterly to determine prioritization of new projects, review progress towards goals, and emerging data. An end-of-year review of projects intended to advance outcome measures and biomarkers is held as part of the Annual FAST Science Summit and includes a larger audience, with the addition of Regulators, biostatisticians, endpoint developers, and other clinicians/academicians.   The ultimate goal of the consortium is to advance regulatory science for Angelman syndrome (AS) to understand, develop, test, and validate different tools that can assess meaningful clinical outcomes for individuals living with Angelman syndrome.  

A-BOM was established in 2016 as a collaborative effort between the leading patient advocacy groups in Angelman syndrome, clinicians with history and knowledge of clinical outcome measures being used to assess individuals with Angelman syndrome, and industry members that were looking to design clinical trials for AS.  It was launched with 5 steering committee members and 25 active participants with a focus on determining the clinical domains of interest that are most impacted in the lives of those living with AS.  The team started by creating a disease concept model which allowed for a gap analysis on available, and useful, outcome measures and biomarkers for AS, as mapped to the key symptoms of interest to caregivers (Figure of domains, endpoints and where we landed) 

Established in 2016: 

• 5 steering committee members 

• 25 participants 

• AS advocacy groups 

• 5 academics 

• 3 pharma companies 

• Zero funded research projects 

• No regulatory engagement 

Focus on priorities for industry/gap analysis on endpoints and biomarkers.     

Current status in 2024:

• 26 steering committee members 

• >300 participants 

  • AS advocacy groups 

  • >25 academics 

  • >15 pharma companies 

• Multiple funded research projects

• Continued regulatory engagement  

 FAST Committed over $4.5M since 2016  

• To create and identify drug development tools that will advance the regulatory science in Angelman syndrome 

• Help reach consensus on the best outcome measures in each functional domain as highlighted in the disease concept model 

• Engage with regulators to ensure the efforts of the A-BOM are aligned with regulatory needs

• Assess existing tools that are fit-for-purpose for Angelman syndrome or adapt existing novel tools using scientific rigor  

• Establish a framework for clinical trial design to benefit ALL sponsors and therapeutic modalities to maximally benefit ALL patients 

The efforts of this consortium have supported the growth, focus, and publication of some of the most robust natural history datasets (NHS) for a rare disease.  This dataset is being utilized by dozens of individuals in the field to understand how to optimally design clinical trials and with the goal to detect meaningful change over time. This NHS alone in the US and Canada has published over 45+ papers from this dataset and has enrolled nearly 600 individuals longitudinally.

Access to the ASA/CGI-S-AS and the CGI-I-AS

The ASA/CGI-S-AS and CGI-I-AS are anchored assessments that are evaluated by a clinician using the totality of clinical data to determine the severity of symptoms and improvement in Angelman syndrome over time. This tool has been used in numerous clinical trials as well as the longitudinal prospective AS Natural History Study (NCT link here). The anchors were developed based on a disease concept model in Angelman syndrome (Willgoss et al, 2021 link here) and corroborated by meaningful symptoms through surveys conducted for the externally led patient focused drug development meeting (EL-PFDD) and include: Sleep, Behavior, Communication (Receptive, Expressive), Motor (Gross/Fine and Oral Motor), and Activities of Daily Living. Each of these anchors are used to create a Clinical Global Impression of Severity and then be used to anchor areas of change in a clinical trial setting.

If you are interested in utilizing the Angelman Syndrome Severity Assessment (ASA)/Clinical Global Impression of Severity-Angelman Syndrome (GTX CGI-S-AS) and/or the Clinical Global Impression Assessment of Improvement-Angelman Syndrome (GTX CGI-S/I-AS) scales, as developed by GeneTx Biotherapeutics LLC and Ultragenyx Pharmaceutical Inc., please send an inquiry email to abom@cureangelman.org and this can be provided.

The A-BOM plays a pivotal role in the current era of the Angelman Syndrome Natural History Study through funding and oversight by a sub-set of the membership. 

• Measuring What Matters to Individuals with Angelman Syndrome and Their Families: Development of a Patient-Centered Disease Concept Model - PubMed (nih.gov) 

• Validation of the Observer-Reported Communication Ability (ORCA) Measure for Individuals With Angelman Syndrome - PubMed (nih.gov) 

• Understanding reliability of the observer-reported communication ability measure within Angelman syndrome through the lens of generalizability theory - PubMed (nih.gov) 

• Developmental Skills of Individuals with Angelman Syndrome Assessed Using the Bayley-III - PubMed (nih.gov) 

• Developmental milestones and daily living skills in individuals with Angelman syndrome - PubMed (nih.gov) 

• Delta power robustly predicts cognitive function in Angelman syndrome - PubMed (nih.gov) 

• Quantitative measures of motor development in Angelman syndrome - PubMed (nih.gov) 

• Qualitative Insights into Key Angelman Syndrome Motor Related Concepts Reported by Caregivers-A Thematic Analysis of Semi-Structured Interviews - PubMed (nih.gov) 

• Development of an adapted Clinical Global Impression scale for use in Angelman syndrome - PMC (nih.gov) 

• Developing Angelman syndrome-specific clinician-reported and caregiver-reported measures to support holistic, patient-centered drug development - PubMed (nih.gov)