Report From the Amyloidosis Forum Scientific Workshop

The Amyloidosis Forum, a Public Private Partnership with ARC and FDA, hosted the workshop on 22nd January,  as part of an ongoing process to develop novel endpoints for clinical trial in AL amyloidosis.

In 2020, the Amyloidosis Forum launched a series of meetings focused on Novel Endpoints and Analyses for Clinical Trials in AL amyloidosis. Following the first meeting held in October 2020, specialized working groups in the areas of cardiac, hematological, renal, and other organ systems were formed. Additional working groups reviewed health-related quality of life measures and statistical approaches to analysis of clinical trial data. Each working group was comprised of leading physicians, patient representatives, statisticians, and representatives from the FDA, MHRA, and pharmaceutical companies. A list of working group leaders and members is available at https://amyloidosisforum.org/workshop-panelists.

The second meeting of the series took place on January 22nd, 2021, in a virtual scientific workshop format moderated by Sarah Cairns‑Smith, Chair of the Amyloidosis Research Consortium (ARC). More than 140 attendees logged on to view presentations and pose questions to the working groups during moderated discussions. The agenda can be viewed at: https://amyloidosisforum.org/workshop-agenda.

The meeting was kicked off by Isabelle Lousada (CEO and Founder of ARC), Dr. Preston Dunnmon (US Food & Drug Administration), and Dr. Cairns-Smith who reviewed the multi-organ involvement in AL amyloidosis and provided an overview of the goals and structure of the meeting series. For context, Dr. James Signorovitch (Analysis Group, Inc.) introduced the concept of a broad “toolbox” of clinical trial endpoints that can be used to develop a multi-domain composite endpoint based on the drug under development and the population studied in a particular clinical trial.

Each specialized working group presentation began with comments by a patient representative to better understand the patient experience:

Mackenzie Boedicker (Founder, Mackenzie’s Mission) described debilitating side effects of traditional AL amyloidosis treatments and highlighted the need for more, less toxic treatment options.
Isabelle Lousada (ARC) summarized cardiac symptoms and unmet medical need for life‑saving therapies in patients with cardiac involvement.
Dena Heath (Northern California Support Group) discussed the symptoms of renal involvement and the burden of dialysis and nutrition management.
Kathy Koontz provided patient perspective on liver and gastrointestinal symptoms as well as peripheral neuropathy as a side effect of treatment.
Paula Schmitt (Amyloidosis Support Groups) summarized the devastating impact of an AL amyloidosis diagnosis and negative impacts of the disease and treatments on health-related quality of life.

Each working group prioritized organ-specific endpoints for use in AL amyloidosis clinical trials. Presentations were given by the following working group leaders on behalf of their respective working group:

Angela Dispenzieri (Mayo Clinic), Hematology
Mathew S. Maurer (Columbia University), Cardiac
Nelson Leung (Mayo Clinic), Renal
Michelle Mauermann (Mayo Clinic), Nerve/Autonomic/Liver/Gastrointestinal
Vaishali Sanchorawala (Boston University), Health Related Quality of Life

Each working group’s recommendations were based on a review of scientific literature, input from patient perspectives, clinical practice, and regulatory precedent. Following each presentation, attendees were able to discuss recommendations and align around prioritized endpoints.

The workshop concluded with Dr. Signorovitch reviewing statistical methods and considerations for development of a composite endpoint in AL amyloidosis clinical trials. The overall goal is to facilitate drug development and allow enrollment of patients likely to benefit from therapy despite involvement of different organs. Next steps involve further analysis and review of the working group recommendations. The statistical working group will then evaluate composite endpoints using available clinical trial datasets.  Finally, the statistical working group will construct a “toolbox” of endpoints for use by sponsors of clinical research trials and regulators and present a proposal at the third meeting of the series.

An archived version of this workshop and other Amyloidosis Forum events can be found at https://amyloidosisforum.org. Information about upcoming meetings, with dates and agendas will be announced in the near future.

About the Amyloidosis Forum

The Amyloidosis Forum is an initiative created by the Amyloidosis Research Consortium (ARC) in collaboration with the US Food and Drug Administration (FDA). This fits within the framework of our Public Private Partnership established to bridge gaps in knowledge and enhance the amyloidosis drug development process. The PPPs efforts are led by Isabelle Lousada, CEO and Founder of ARC, and Dr. Dunnmon who serves as the PPP liaison to FDA. To learn more about the Amyloidosis Forum, please visit: https://amyloidosisforum.org.