Potential Pathways for Development of Imaging Endpoints for Clinical Trials in AL and ATTR Amyloidosis

November 18, 2022

This hybrid in-person and virtual meeting of the Amyloidosis Forum explored the different imaging modalities being used in AL/ATTR amyloidosis. The discussion sought to identify knowledge gaps impeding their implementation as validated tools that could serve as endpoints adequate for drug approval in interventional clinical trials.

Participants including clinicians, FDA (DIRM, DCN, DHM), MHRA, NIH, industry partners, patients, and the Amyloidosis Research Consortium (ARC) highlighted what was needed to enable the use of imaging measures as tools for determining study eligibility, for assessing safety throughout the study, and for use as clinical endpoints for regulatory decision making in trials of new therapeutics for AL and ATTR amyloidosis.

Public Private Partnership with FDA

Faculty

Moderators

Isabelle Lousada
 
Host
Founder and CEO
Amyloidosis Research Consortium
BIO+
Rosalyn Adigun
MD, PharmD, MS
Host
Medical Officer, Division of Cardiology and Nephrology
U.S. Food and Drug Administration
BIO+
Preston Dunnmon
MD, MBA, FACP, FACC
Moderator
Vice President, Data Science, Cardiovascular, Metabolism, & Pulmonary Hypertension
Janssen Research and Development
BIO+
Sharmila Dorbala
MD, MPH, MASNC
Moderator & Meeting Chair
Director, Nuclear Cardiology
Brigham and Women’s Hospital
BIO+

Speakers

Andrew Stephens, MD, PhD
Chief Medical Officer
Life Molecular Imaging (LMI)
BIO+
Ahmad Masri, MD MS
Director, Hypertrophic Cardiomyopathy Center; Director, Cardiac Amyloidosis Program; & Assistant Professor of Medicine
Oregon Health & Science University
BIO+
Ashutosh Wechalekar, MBBS, MD, FRCP, FRCPath, DM
Senior Lecturer & Honorary Consultant Hematologist
University College London
BIO+
August Hofling, MD, PhD
Deputy Director, Division of Imaging and Radiation Medicine in the Center for Drug Evaluation and Research
U.S. Food and Drug Administration
BIO+
Brett W Sperry, MD
Cardiology, Heart Failure and Transplantation Cardiology
Saint Luke's Mid America Heart Institute
BIO+
Christophe Sirac, PhD
Professor
University of Limoges, France
Clemens Mittmann, MD
Federal Institute for Drugs and Medical Devices (Germany)
BIO+
Cristina C. Quarta, MD PhD
Senior Director, Clinical Development and Translational Sciences
Alexion, AstraZeneca Rare Disease
BIO+
Cynthia Welsh, MD
Medical Officer, Rare Diseases Team; Division of Rare Diseases and Medical Genetics
Center for Drug Evaluation and Research (CDER), Food and Drug Administration (FDA)
BIO+
Frederick L. Ruberg, MD
Associate Chief, Academic Affairs, Section of Cardiovascular Medicine & Associate Professor of Medicine and Radiology
Boston University School of Medicine, Boston Medical Center
BIO+
Grace Lin, MD, MBA
Advanced Heart Failure Cardiologist and Echocardiographer
Mayo Clinic
BIO+
James Signorovitch, PhD
Managing Principal, Health Economics and Outcomes Research, Epidemiology, & Biostatistics
Analysis Group, Inc.
BIO+
Jean-Michel Race, MD
Agence nationale de sécurité du médicament et des produits de santés (France)
Jens Sörenson, MD, PhD
Professor
Uppsala University, Sweden
John Vest, M.D.
SVP, Clinical Research
Alnylam Pharmaceuticals
BIO+
Jonathan S. Wall, PhD
Professor
University of Tennessee Medical Center, Knoxville
BIO+
Joseph Rajendran, MD, FASNC and FACNM
Medical Officer, Division of Imaging and Radiation Medicine
U.S. Food and Drug Administration
BIO+
Justin L. Grodin, MD, MPH, FACC, FHFSA
Medical Director, Internal Medicine Clinical Trials Unit Co-director
UT Southwestern Multidisciplinary Amyloidosis Program
BIO+
Kevin Alexander, MD, FACC, FHFSA
Cardiologist
Stanford Amyloid Center
BIO+
Krishna Prasad, MD
Deputy Director, Innovative Medicines, HQA/Licensing
Medicines and Healthcare Products Regulatory Agency (MHRA), United Kingdom
BIO+
Marianna Fontana, MD, PhD, FRCP
Honorary Consultant Cardiologist & Director of CMR
UCL Royal Free Hospital
BIO+
Mathew S. Maurer, MD
Cardiologist & Medical Director
The HCM Center at New York-Presbyterian Hospital/Columbia University Medical Center
BIO+
Michael Jerosch-Herold, PhD
Director of Cardiac Imaging Physics
Brigham and Women’s Hospital
BIO+
Michela Brambatti, MD, MS, FESC
Director, Clinical Development
Ionis Pharmaceuticals, Inc.
BIO+
Michele Emdin, MD, PhD
Director of Cardiology Division
Fondazione G. Monasterio
BIO+
Nicole Gormley, MD
Division Director for the Division of Hematologic Malignancies II
U.S. Food and Drug Administration
BIO+
Norman Stockbridge, MD, PhD
Director of the Division of Cardiology and Nephrology in the Center for Drug Evaluation and Research
U.S. Food and Drug Administration
BIO+
Omar F. Abou Ezzeddine, M.D., C.M., M.S.
Assistant Professor of Medicine; Consultant, Department of Cardiovascular Medicine, Division of Circulatory Failure, and Division of Nuclear Cardiology
Mayo Clinic College of Medicine and Science
BIO+
Prem Soman, MD, PhD, FACC, FRCP
Professor of Medicine and Clinical & Translational Science
University of Pittsburgh Medical Center
BIO+
Rodney H. Falk, MD
Associate Professor, Division of Cardiovascular Medicine
Harvard Medical School
BIO+
Sarah Cuddy, MB BCh BAO
Cardiologist, Amyloidosis Program
Brigham and Women’s Hospital
BIO+
Spencer Guthrie, MPH, MBA
Co-Founder & COO
Attralus, Inc.
BIO+
Vandana Sachdev, MD
Senior Research Clinician and Director of the Echocardiography Laboratory in the Division of Intramural Research
National Heart, Lung, and Blood Institute
BIO+

Agenda

8:45 am
Welcome and Introductions
Isabelle Lousada & Rosalyn Adigun
8:55 am
Overview: The Central Role of Imaging-Based Biomarkers
Sharmila Dorbala
9:05 am
Animal Models for AL and ATTR Amyloidosis and the Need for Imaging
Christophe Sirac & Kevin Alexander
9:15 am
Biomarkers in Drug Development
Preston Dunnmon
9:25 am
Echocardiography: AL and ATTR Amyloidosis
Rodney Falk, Ashutosh Wechalekar, Grace Lin, Sarah Cuddy, & Cristina Quarta
9:55 am
Cardiac MRI: AL and ATTR Amyloidosis
Marianna Fontana, Frederick L. Ruberg, Justin L. Grodin, Michael Jerosch-Herold, & Michela Brambatti
10:25 am
Break
10:35 am
Molecular Imaging of Amyloidosis-SPECT: ATTR Amyloidosis
Sharmila Dorbala, Mathew S. Maurer, Brett W. Sperry, Omar Abou Ezzeddine, Prem Soman, & John Vest
11:05 am
Molecular Imaging of Amyloidosis-PET: AL and ATTR Amyloidosis
Sharmila Dorbala, Michele Emdin, Jens Sörenson, Jonathan S. Wall, Spencer Guthrie, & Andrew Stephens
11:35 am
Connecting Changes in Amyloid Through Imaging with Changes in Cardiac Events, Functional Measures, & Health-Related Quality of Life
Ashutosh Wechalekar & Brett W. Sperry, moderated by Sarah Cuddy
11:55 am
Moderated Discussion: Standardization of Imaging in AL/ATTR Research
All

12:25 pm
Lunch
1:05 pm
Laying the Groundwork for Qualifying Images as Potential Clinical Outcome Surrogates: How to Get There from Here
Preston Dunnmon
1:10 pm
Patient Perspectives: The Value of Imaging
Isabelle Lousada
1:20 pm
Case Study from Another Rare Disease: Mavacamten in Symptomatic Obstructive Hypertrophic Cardiomyopathy (oHCM)
Ahmad Masri
1:30 pm
Images as Predictive Biomarkers (Trial Endpoint Surrogates): Current Thinking by the Health Authorities
Norman Stockbridge, Rosalyn Adigun, Joseph Rajendran, August Hofling, Nicole Gormley, Cynthia Welsh, Krishna Prasad, Clemens Mittmann, & Jean-Michel Race
2:05 pm
NIH HeartShare Study and BioData Catalyst
Vandana Sachdev
2:20 pm
Break
2:30 pm
Moderated Discussion: Potential Pathway(s) for Imaging Biomarker Development in AL and ATTR Amyloidosis
All
3:30 pm
Closing Remarks
Isabelle Lousada & Rosalyn Adigun
3:40 pm
Adjourn

Recordings

Recording of the Morning Sessions

Moderated by the meeting chair, Sharmila Dorbala MD, MPH, MASNC, Director of Nuclear Cardiology at Brigham and Women’s Hospital.
Recording of the Afternoon Sessions

Moderated by Preston Dunnmon MD, MBA, FACP, FACC, Vice President of Data Science, Cardiovascular, Metabolism, & Pulmonary Hypertension at Janssen Research and Development.

How We Work

The Amyloidosis Forum has established a collaborative framework with appropriate stakeholders, including government, academic, scientific, patient, and industry organizations, to foster scientific collaborations. The Forum convenes regular meetings and has defined both workstreams and working groups to focus on key areas. The Forum is committed to publishing the outcomes from these initiatives.

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About the Forum

The Amyloidosis Forum is a public-private partnership between the Amyloidosis Research Consortium (ARC) and the U.S. Food and Drug Administration (FDA). The overarching goal of the Forum is to accelerate the advancement of new therapeutics by addressing scientific gaps and unmet research needs in the precompetitive domain that aid in the evaluation of the efficacy and safety of new therapies.