TY - JOUR
T1 - Advancing Transthyretin Amyloidosis Drug Development in an Evolving Treatment Landscape
T2 - Amyloidosis Forum Meeting Proceedings
AU - On behalf of the Amyloidosis Forum Meeting Panelists
AU - Maurer, Mathew S.
AU - Soman, Prem
AU - Hernandez, Adrian
AU - Garcia-Pavia, Pablo
AU - Signorovitch, James
AU - Wei, L. J.
AU - Hanna, Mazen
AU - Ruberg, Frederick L.
AU - Kittleson, Michelle
AU - Kazi, Dhruv
AU - Dorbala, Sharmila
AU - Hsu, Kristen
AU - Lousada, Isabelle
AU - Adigun, Rosalyn
AU - Dunnmon, Preston
AU - Kelly, Jeffery
AU - Gillmore, Julian
AU - Masri, Ahmad
AU - Morris, Alanna
AU - Dispenzieri, Angela
AU - Berk, John
AU - Ferdinand, Keith
AU - Shah, Keyur
AU - McCausland, Kristen
AU - Henshaw, Lynnette
AU - Grogan, Martha
AU - Azzarone, Megan
AU - Polydefkis, Michael
AU - Fiuzat, Mona
AU - Bullock-Palmer, Renee P.
AU - Booth, Benjamin
AU - Gandotra, Charu
AU - Mittmann, Clemens
AU - Welsh, Cynthia
AU - Dawoud, Dalia
AU - Zouridakis, Emmanouil
AU - Cunningham, Francesca
AU - Race, Jean Michel
AU - Li, Jie
AU - Sakushima, Ken
AU - Jawidzik, Laura
AU - Campbell, Michelle
AU - Rahman, Motiur
AU - Stockbridge, Norman L.
AU - Lloyd, Rhea
AU - Bent, Robyn
AU - Kuehn, Sylvia
AU - Chambers, Wiley
AU - Slugg, Andrew
AU - Angeli, Franca
N1 - Publisher Copyright:
© The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature 2024.
PY - 2024/7
Y1 - 2024/7
N2 - Introduction: Hereditary transthyretin amyloidosis (ATTRv, also referred to as hATTR; ORPHA 271861) and wild-type ATTR amyloidosis (ATTRwt; ORPHA 330001) are rare, progressive, systemic protein misfolding disorders with heterogeneous clinical presentations. ATTRv and ATTRwt amyloidosis are characterized by the deposition of amyloid fibrils in multiple organs including the heart, nerves, eyes, and soft tissues. The management of ATTR amyloidosis is complex because of its multisystemic nature and progression despite available treatment options. Morbidity is high and there are many unmet medical needs for patients. While contemporary ATTR amyloidosis cohorts are diagnosed earlier, have lower risk disease and lower mortality compared with the previous era, these advances coupled with the emergence of effective disease-modifying therapies have confounded the design of future prospective clinical trials and interpretation of historical control data. Main Body: The Amyloidosis Forum is a public–private partnership between the US Food and Drug Administration Center for Drug Evaluation and Research and the nonprofit Amyloidosis Research Consortium (www.arci.org). This article summarizes proceedings from the 21 June 2023 Amyloidosis Forum on advancing drug development in ATTR amyloidosis in an evolving treatment landscape. The Forum focused on elements of clinical trial design to address these challenges and discussed their strengths and weaknesses from multiple stakeholder perspectives (i.e., patient, sponsor, statistician, clinician, and regulatory authorities). Conclusion: Given rapid evolution of natural history in ATTR amyloidosis, the utility of historical control data is limited. Leveraging contemporary real-world data is essential for clinical trial design. Evidence generation from clinical trials should address clinically relevant questions. Key factors in successful trial design must be informed by up-to-date data on natural history, prognostic factors, clinically meaningful thresholds, and sharing available clinical trial data. The Amyloidosis Forum includes the community of patients with ATTR amyloidosis, the physicians who treat them, and the sponsors and regulators who collectively stand ready to support further studies in order to develop novel effective therapies.
AB - Introduction: Hereditary transthyretin amyloidosis (ATTRv, also referred to as hATTR; ORPHA 271861) and wild-type ATTR amyloidosis (ATTRwt; ORPHA 330001) are rare, progressive, systemic protein misfolding disorders with heterogeneous clinical presentations. ATTRv and ATTRwt amyloidosis are characterized by the deposition of amyloid fibrils in multiple organs including the heart, nerves, eyes, and soft tissues. The management of ATTR amyloidosis is complex because of its multisystemic nature and progression despite available treatment options. Morbidity is high and there are many unmet medical needs for patients. While contemporary ATTR amyloidosis cohorts are diagnosed earlier, have lower risk disease and lower mortality compared with the previous era, these advances coupled with the emergence of effective disease-modifying therapies have confounded the design of future prospective clinical trials and interpretation of historical control data. Main Body: The Amyloidosis Forum is a public–private partnership between the US Food and Drug Administration Center for Drug Evaluation and Research and the nonprofit Amyloidosis Research Consortium (www.arci.org). This article summarizes proceedings from the 21 June 2023 Amyloidosis Forum on advancing drug development in ATTR amyloidosis in an evolving treatment landscape. The Forum focused on elements of clinical trial design to address these challenges and discussed their strengths and weaknesses from multiple stakeholder perspectives (i.e., patient, sponsor, statistician, clinician, and regulatory authorities). Conclusion: Given rapid evolution of natural history in ATTR amyloidosis, the utility of historical control data is limited. Leveraging contemporary real-world data is essential for clinical trial design. Evidence generation from clinical trials should address clinically relevant questions. Key factors in successful trial design must be informed by up-to-date data on natural history, prognostic factors, clinically meaningful thresholds, and sharing available clinical trial data. The Amyloidosis Forum includes the community of patients with ATTR amyloidosis, the physicians who treat them, and the sponsors and regulators who collectively stand ready to support further studies in order to develop novel effective therapies.
KW - Clinical trial design
KW - Drug development
KW - Rare diseases
KW - Transthyretin amyloidosis
UR - http://www.scopus.com/inward/record.url?scp=85195178523&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85195178523&partnerID=8YFLogxK
U2 - 10.1007/s12325-024-02891-0
DO - 10.1007/s12325-024-02891-0
M3 - Review article
C2 - 38833142
AN - SCOPUS:85195178523
SN - 0741-238X
VL - 41
SP - 2723
EP - 2742
JO - Advances in Therapy
JF - Advances in Therapy
IS - 7
ER -