ACTION A2D2 Consortium

  • jump-linkAccelerating Innovation in Coronary Artery Disease Drug Development
  • jump-linkWhy NCPV?

    • ACTION A2D2 Overview

    Accelerating Innovation in Coronary Artery Disease Drug Development

    The ACTION A2D2 Initiative (Atherosclerosis Computed Tomographic Imaging to Optimize New Drug Development) is a global multi stakeholder effort coordinated by CAD Frontiers, working toward the regulatory qualification of non-calcified plaque volume (NCPV) as a drug development tool through the U.S. FDA Biomarker Qualification Program.

    Why NCPV?

    Non-calcified plaque volume, measured via coronary CT angiography (CCTA), is a modifiable, quantifiable marker of coronary artery disease (CAD). Unlike calcified plaque, NCPV has been shown to regress with effective therapy and is associated with major adverse cardiovascular events (MACE), making it a compelling candidate for:

    • Prognostic Enrichment: Selecting higher-risk participants in clinical trials

    • Surrogate Endpoint Development: Evaluating early drug efficacy signals

    In 2024, the ACTION A2D2 Consortium submitted a Letter of Intent to the U.S. FDA, which was officially accepted into the CDER Biomarker Qualification Program in December 2024 (DDT-BMQ-000161). The initiative is now advancing toward submission of a full Qualification Plan.

  • jump-linkAnalytic Validity Working Group
  • jump-linkClinical Validity Working Group

    • Working Groups: Driving Scientific Rigor and Regulatory Readiness

    To meet the evidence requirements for FDA biomarker qualification, two expert-led working groups are leading the charge:

    Analytic Validity Working Group

    Demonstrate that NCPV can be measured accurately and reproducibly across imaging centres, vendors, and platforms.

    Co-Leads: Professor Pamela S. Douglas (Duke University) and Professor Matthew Budoff (Harbor-UCLA)

    Membership:

    • Ron Blankstein (Brigham and Women’s Hospital)

    • Lohendran Baskaran (National Heart Centre Singapore)

    • Melissa Daubert (Duke University)

    • Mark Dewey (Charité Berlin)

    • Damini Dey (Cedars-Sinai Medical Center)

    • Maros Ferencik (Oregon Health & Science University)

    • Charu Gandotra (U.S. FDA)

    • Stuart Grieve (University of Sydney)

    • Jeff Siegel (U.S. FDA)

    • Todd Villines (University of Virginia)

    • Michelle Williams (University of Edinburgh)

    Clinical Validity Working Group

    Establish the clinical utility of NCPV as a prognostic biomarker by demonstrating its association with cardiovascular outcomes and response to therapy.

    Co-Leads: Professor Kelley R. Branch (University of Washington) and Professor Jonathon Leipsic (University of British Columbia)

  • jump-linkFinancial Supporters
  • jump-linkSociety Members

    • Support the Initiative

    Financial Supporters

    The ACTION A2D2 Consortium is made possible through the generous contributions of our partners from industry, supporting the scientific coordination, working group operations, and stakeholder engagement.

    Society Members

    We are proud to be joined by the following professional societies, ensuring transparency of the effort and efficiency of communications.

    • American Heart Association (AHA)

    • European Association of Cardiovascular Imaging (EACVI)

    • North American Society for Cardiovascular Imaging (NASCI)