Amyloidosis Research Consortium Inc

THE AMYLOIDOSIS FORUM: CROSS STAKEHOLDER WORKING GROUP PROJECTS TO ACCELERATE DRUG DEVELOPMENT IN AL AND ATTR AMYLOIDOSIS - PROJECT SUMMARY/ABSTRACT THE AMYLOIDOSIS RESEARCH CONSORTIUM (ARC), ESTABLISHED IN 2015, IS A PATIENT-LED NONPROFIT ORGANIZATION. ARC’S MISSION 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 WITH THE US FOOD AND DRUG ADMINISTRATION (FDA) KNOWN AS THE AMYLOIDOSIS FORUM TO BRIDGE SCIENTIFIC GAPS IN DRUG DEVELOPMENT FOR THE TREATMENT OF AMYLOIDOSIS. THE AMYLOIDOSIS FORUM SEEKS TO LEVERAGE THE EXPERTISE AND RESOURCES OF DIVERSE STAKEHOLDERS FOR THE CONDUCT OF MUTUALLY BENEFICIAL SCIENTIFIC ACTIVITIES IN THE PRECOMPETITIVE DOMAIN TO SUPPORT BRINGING NEW, SAFE AND EFFICACIOUS THERAPIES TO PATIENTS WITH AMYLOIDOSIS. COLLABORATIVE EFFORTS ACROSS STAKEHOLDERS AND INNOVATIVE APPROACHES ARE ESSENTIAL TO PROPEL THE FUTURE DEVELOPMENT OF EFFECTIVE THERAPIES FOR MULTI-SYSTEMIC DISEASES LIKE IMMUNOGLOBULIN LIGHT CHAIN (AL) AND TRANSTHYRETIN (ATTR) AMYLOIDOSIS. THE PROPOSED CONFERENCE, TO BE HELD AT THE FDA WHITE OAK CAMPUS, WILL PROVIDE AN OPPORTUNITY FOR PRIORITIZED WORKING GROUPS LAUNCHED THROUGH THE AMYLOIDOSIS FORUM TO SHARE THEIR RESEARCH AND ENGAGE WITH DIVERSE STAKEHOLDERS TO SEEK FEEDBACK AND INSIGHT THAT WILL ENABLE THEM TO STRENGTHEN THEIR RESEARCH. THESE COLLABORATIVE WORKING GROUPS ARE FOCUSED ON FOUR PRIORITY AREAS: IMAGING STANDARDIZATION, IDENTIFICATION OF PROGNOSTIC FACTORS, DEVELOPMENT OF CLINICAL ENDPOINTS, AND ACCELERATING ACCESS TO DATA-DRIVEN INSIGHTS FROM COMPLETED TRIALS IN AL AND ATTR AMYLOIDOSIS. THIS MEETING, THE AMYLOIDOSIS FORUM: CROSS STAKEHOLDER WORKING GROUP PROJECTS TO ACCELERATE DRUG DEVELOPMENT IN AL AND ATTR AMYLOIDOSIS, WILL AIM TO DO THE FOLLOWING: SPECIFIC AIM 1: ENGAGE DIVERSE STAKEHOLDERS TO INFORM AND STRENGTHEN WORKING GROUP RESEARCH STRATEGIES AND PROJECTS THAT WILL ADDRESS SCIENTIFIC AND REGULATORY GAPS REQUIRED TO ADVANCE DRUG DEVELOPMENT. • CRITICALLY EVALUATE AND DISCUSS RESEARCH UPDATES PROVIDED BY THE AMYLOIDOSIS FORUM WORKING GROUPS. • PRESENT DIVERSE FEEDBACK ON THE DESIGN OF PROPOSED COLLABORATIVE RESEARCH STUDIES. SPECIFIC AIM 2: PROVIDE A COLLABORATIVE OPPORTUNITY FOR STAKEHOLDERS TO CONVEY THEIR PERSPECTIVES ON FUTURE PRIORITIES AND RESEARCH DIRECTION. • EVALUATE AND ALIGN STAKEHOLDER PRIORITIES FOR FUTURE RESEARCH PROJECTS. SPECIFIC AIM 3: ENABLE EARLY-CAREER PROFESSIONALS WITH OPPORTUNITIES TO NETWORK WITH EXPERIENCED AMYLOIDOSIS RESEARCHERS. • PROVIDE EARLY CAREER PROFESSIONALS WITH BROAD PERSPECTIVES ACROSS THE AMYLOIDOSIS THERAPEUTIC DEVELOPMENT SPECTRUM AND AN OPPORTUNITY TO ENGAGE WITH EXPERIENCED RESEARCH PROFESSIONALS.

THE AMYLOIDOSIS FORUM: ADVANCING DRUG DEVELOPMENT IN ATTR AMYLOIDOSIS IN AN EVOLVING TREATMENT LANDSCAPE. - 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.

ADVANCING DRUG DEVELOPMENT IN AL AMYLOIDOSIS: CAPITALIZING NATURAL HISTORY AND ASSESSING ENDPOINTS - PROJECT SUMMARY AMYLOIDOSIS RESEARCH CONSORTIUM (ARC), A 501(C)(3) NONPROFIT ORGANIZATION FOCUSED ON ACCELERATING THE DEVELOPMENT, APPROVAL, AND ACCESS TO NEW AND INNOVATIVE TREATMENTS FOR AMYLOIDOSIS. IN 2019, ARC ENTERED INTO A PUBLIC PRIVATE PARTNERSHIP (PPP) WITH THE US FOOD AND DRUG ADMINISTRATION (FDA) TO IDENTIFY AND BRIDGE THE SCIENTIFIC GAPS IN DRUG DISCOVERY AND DEVELOPMENT FOR THE TREATMENT OF AL AMYLOIDOSIS. AMYLOIDOSIS IS THE TERM FOR A GROUP OF RARE, PROGRESSIVE AND FATAL MISFOLDED PROTEIN DISEASES. AL AMYLOIDOSIS A RARE AND MULTI-SYSTEMIC DISEASE IN WHICH THERE IS NO APPROVED FDA THERAPY. AL AMYLOIDOSIS IS A DISEASE THAT DISPROPORTIONATELY AFFLICTS OLDER ADULTS AND HAS A POOR PROGNOSIS WHEN DIAGNOSED IN AN ADVANCED STAGE. ALL THE EMERGING THERAPIES ARE AIMED AT TREATING THE UNDERLYING PLASMA CELL DYSCRASIA ARE MOST ADVANTAGEOUS WHEN ADMINISTERED EARLY IN THE COURSE OF THE DISEASE. AS PART OF THE PPP, ARC AND FDA ARE PROPOSING TO HOST THE SECOND IN A SERIES OF CROSS- STAKEHOLDER SCIENTIFIC MEETINGS (WITH INVOLVEMENT FROM PATIENTS, ACADEMIA, INDUSTRY, AND REGULATORY AGENCIES) ENTITLED THE AMYLOIDOSIS FORUM. EACH OF THESE MEETINGS IS FOCUSED ON IDENTIFYING THE KNOWLEDGE GAPS, BARRIERS, AND STRATEGICALLY ADDRESSING THESE TO ADVANCE DRUG DEVELOPMENT IN THIS CHALLENGING DISEASE. THE NEXT PUBLIC MEETING WILL BE HELD ON 12TH NOVEMBER, 2020, ENTITLED: AMYLOIDOSIS FORUM MEETING 2: ADVANCING DRUG DEVELOPMENT IN AL AMYLOIDOSIS: CAPITALIZING NATURAL HISTORY AND ASSESSING ENDPOINTS: FORUM OBJECTIVE 1: NATURAL HISTORY AND ENDPOINT DEVELOPMENT: THE MORNING SESSIONS WILL PROVIDE AN IN DEPTH LOOK AT THE IMPORTANCE OF NATURAL HISTORY FROM ACADEMIA, INDUSTRY AND REGULATORY PERSPECTIVES. THERE WILL BE PRESENTATIONS ON CURRENT SOURCES OF NATURAL HISTORY FROM ACADEMIA, INDUSTRY (PLACEBO DATA) AND OTHER SOURCES, AS WELL AS DISCUSSION ABOUT HOW TO LEVERAGE EXISTING DATASETS TO IDENTIFY MEANINGFUL ENDPOINTS, DISEASE SPECIFIC MEASUREMENTS, AND ULTIMATELY ACCELERATE RESEARCH. FORUM OBJECTIVE 2: ENDPOINT DEVELOPMENT: GIVEN THE COMPLEX MULTI-SYSTEMIC NATURE OF AL AMYLOIDOSIS, ENDPOINT CHOICE IS CHALLENGING. THE SECOND PART OF THE FORUM WILL FOCUS ON ENDPOINT DEVELOPMENT; TRADITIONAL DESIGNS VERSUS NOVEL DESIGNS. SUCH AS HIERARCHICAL OR MULTIMODAL ENDPOINTS, WITH CASE STUDIES FROM INDUSTRY AND FDA. THIS MEETING WILL SEEK TO DEFINE INNOVATIVE APPROACHES TOWARD ENDPOINT DEVELOPMENT INCLUDING CONSIDERATIONS FOR A MULTI-DOMAIN RESPONDER INDEX (MDRI).