The Amyloidosis Forum: Advancing Drug Development in ATTR Amyloidosis in an Evolving Treatment Landscape.

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Project Summary/Abstract The Amyloidosis Research Consortium (ARC), established in 2015, is a patient-led nonprofit organization. The mission of ARC is to build mutually beneficial collaborations between government, academia, industry, patients, and regulatory agencies to systematically address critical barriers and challenges that slow the development of new therapies for systemic amyloidosis. In 2019, ARC entered a public-private partnership (PPP) with the US Food and Drug Administration (FDA) to bridge scientific gaps in drug development, known as the Amyloidosis Forum. The Amyloidosis Forum provides a unique opportunity for the multidisciplinary, cross- stakeholder amyloidosis community to come together to identify and bridge the scientific gaps that act as barriers to drug discovery and development for the treatment different types of amyloidosis. The PPP framework includes convening meetings to align the field, resulting in formalized working groups to accelerate action. In 2022, the PPP obtained approval from the FDA to expand the remit of the Amyloidosis Forum to include transthyretin amyloidosis (ATTR) in recognition of the unmet needs and challenges that prevail in current and future therapeutic development. The first generation of drug approvals in ATTR has reshaped the research landscape creating the need to reconsider how to effectively design trials against a backdrop of treatments that slow progression of the disease. This Forum meeting will set the stage by sharing the advancements, evaluating the impact and unmet needs that currently exist, and identifying key initiatives with the aim of leveraging cross-stakeholder resources to collaboratively act on field-shaping priorities. Addressing themes related to Advancing Drug Development in ATTR in an Evolving Treatment Landscape, our Specific Aims include: Specific Aim 1: Understand the impact of novel treatments and the current unmet needs in patients with ATTR.  Review and discuss advances in the field of ATTR including approaches to treatment and the selection of new therapies, the assessment of the role of combination therapies, and how progression and response is measured in real-world settings.  Bring greater context to the above themes through patient participation, particularly with respect to persistent healthcare inequities. Specific Aim 2: Define new approaches to designing clinical trials in ATTR.  Establish a common understanding of the current and anticipated challenges facing drug development in ATTR for the next generation of clinical development programs.  Assess the potential role of biomarkers and evidence gaps, evaluate the strength of various biomarkers, endpoints, and trial designs, and define collaborative approaches to assessing these for application in trial design. Specific Aim 3: Outline regulatory approval and reimbursement challenges and define forward-looking action plans.  Provide an understanding of the current and anticipated challenges facing regulatory approvals and reimbursement in ATTR.  Outline actions to address these challenges for the next generation of therapies.