TY - JOUR
T1 - Characteristics of Patients with Hereditary Transthyretin Amyloidosis-Polyneuropathy (ATTRv-PN) in NEURO-TTRansform, an Open-label Phase 3 Study of Eplontersen
AU - Coelho, Teresa
AU - Waddington Cruz, Márcia
AU - Chao, Chi Chao
AU - Parman, Yeşim
AU - Wixner, Jonas
AU - Weiler, Markus
AU - Barroso, Fabio A.
AU - Dasgupta, Noel R.
AU - Jung, Shiangtung W.
AU - Schneider, Eugene
AU - Viney, Nicholas J.
AU - Dyck, P. James B.
AU - Ando, Yukio
AU - Gillmore, Julian D.
AU - Khella, Sami
AU - Gertz, Morie A.
AU - Obici, Laura
AU - Berk, John L.
N1 - Funding Information:
This study was sponsored by Ionis Pharmaceuticals, Inc., Carlsbad, CA, USA. Medical writing and editorial support were provided by Sandra Westra, PharmD, and Jessica D. Herr, PharmD, of Peloton Advantage, LLC, an OPEN Health company, and funded by Ionis Pharmaceuticals, Inc., Carlsbad, CA, USA. Ionis Pharmaceuticals, Inc., also provided funding for the journal’s Rapid Service Fee.
Funding Information:
Teresa Coelho: has received financial support to attend scientific meetings from Akcea, Ionis, Alnylam, Pfizer, and Biogen, and receives no personal speaker or consultant honoraria. Márcia Waddington Cruz: has received advisory board and speaker honoraria and financial support for conference attendance from Akcea, Alnylam, Pfizer, and Sobi. Chi-Chao Chao: reports no conflicts of interest. Yeşim Parman: has lectured for Alnylam and Pfizer. Jonas Wixner: has received advisory board and speaker honoraria and financial support for conference attendance from Akcea, Alnylam, and Pfizer. Markus Weiler: has received advisory board and speaker honoraria and financial support for conference attendance from Akcea, Alnylam, Pfizer, and Sobi. Fabio A. Barroso: has received advisory board and speaker honoraria and financial support for conference attendance from Alnylam, Pfizer, and PTC Therapeutics. Noel R. Dasgupta: has received advisory board honoraria from Ionis, Akcea, Alnylam, Pfizer, Eidos, and Intellia, and speaker honoraria from Akcea, Alnylam, and Pfizer. Shiangtung W. Jung: is employed by Ionis. Eugene Schneider: is employed by Ionis. Nicholas J. Viney: is employed by Ionis. P. James B. Dyck: reports no conflicts of interest. Yukio Ando: reports no conflicts of interest. Julian D. Gillmore: has served as an advisor for Alnylam, Ionis, Intellia, Eidos, Pfizer, and ATTRalus. Sami Khella: has served as a consultant to Alnylam, Ionis, Sobi, Pfizer, and Eidos. Morie A. Gertz: has received personal fees from Aptitude, Celgene, Ionis, Akcea, Janssen, Johnson & Johnson, Physicians Education Resource, Prothena, Research to Practice, and Sanofi; health grants and personal fees from Ashfield; financial support for meetings from Juno and Sorrento; fees for serving on a data safety monitoring board from AbbVie; fees for the development of educational materials from i3Health. Laura Obici: has received advisory board and speaker honoraria from Akcea, Alnylam, Pfizer, and Sobi. John L. Berk: has received honoraria for serving on advisory boards for Akcea, Ionis and Eidos, BridgeBio; scientific advisory boards for Corino, and received remotely, Intellia.
Publisher Copyright:
© 2022, The Author(s).
PY - 2023/2
Y1 - 2023/2
N2 - Introduction: Hereditary transthyretin (ATTRv) amyloidosis is a rare, severe, progressive, debilitating, and ultimately fatal disease caused by systemic deposition of transthyretin (TTR) amyloid fibrils. ATTRv amyloidosis occurs in both males and females. Eplontersen (ION-682884), a ligand-conjugated antisense oligonucleotide designed to degrade hepatic TTR mRNA, is being evaluated for the treatment of ATTRv amyloidosis with polyneuropathy (ATTRv-PN) in the phase 3, international, multicenter, open-label NEURO-TTRansform study (NCT04136184). To describe the study population of this pivotal trial, here we report the baseline characteristics of patients enrolled in the NEURO-TTRansform study. Methods: Patients eligible for NEURO-TTRansform were 18–82 years old with a diagnosis of ATTRv-PN and Coutinho stage 1 (ambulatory without assistance) or stage 2 (ambulatory with assistance) disease; documented TTR gene variant; signs and symptoms consistent with neuropathy associated with ATTRv; no prior liver transplant; and New York Heart Association (NYHA) functional class I or II. Results: The NEURO-TTRansform study enrolled 168 patients across 15 countries/territories (North America, 15.5%; Europe, 38.1%; South America/Australia/Asia, 46.4%). At baseline, the study cohort had a mean age of 52.8 years, 69.0% of patients were male, and 78.0% of patients were White. The V30M variant was most prevalent (60.1% of patients), and prevalence varied by region. Overall, 56.5% and 17.3% of patients had received previous treatment with tafamidis or diflunisal, respectively. A majority of patients (79.2%) had Coutinho stage 1 disease (unimpaired ambulation) and early (before age 50) disease onset (53.0%). Time from diagnosis to enrollment was 46.6 (57.4) months (mean [standard deviation]). Most patients had a baseline polyneuropathy disability (PND) score of I (40.5%) or II (41.1%), and the mean modified Neuropathy Impairment Score + 7 (mNIS + 7) was 79.0. Conclusion: The recruited population in the ongoing NEURO-TTRansform study has global representation characteristic of contemporary clinical practice. Trial Registration: ClinicalTrials.gov identifier NCT04136184.
AB - Introduction: Hereditary transthyretin (ATTRv) amyloidosis is a rare, severe, progressive, debilitating, and ultimately fatal disease caused by systemic deposition of transthyretin (TTR) amyloid fibrils. ATTRv amyloidosis occurs in both males and females. Eplontersen (ION-682884), a ligand-conjugated antisense oligonucleotide designed to degrade hepatic TTR mRNA, is being evaluated for the treatment of ATTRv amyloidosis with polyneuropathy (ATTRv-PN) in the phase 3, international, multicenter, open-label NEURO-TTRansform study (NCT04136184). To describe the study population of this pivotal trial, here we report the baseline characteristics of patients enrolled in the NEURO-TTRansform study. Methods: Patients eligible for NEURO-TTRansform were 18–82 years old with a diagnosis of ATTRv-PN and Coutinho stage 1 (ambulatory without assistance) or stage 2 (ambulatory with assistance) disease; documented TTR gene variant; signs and symptoms consistent with neuropathy associated with ATTRv; no prior liver transplant; and New York Heart Association (NYHA) functional class I or II. Results: The NEURO-TTRansform study enrolled 168 patients across 15 countries/territories (North America, 15.5%; Europe, 38.1%; South America/Australia/Asia, 46.4%). At baseline, the study cohort had a mean age of 52.8 years, 69.0% of patients were male, and 78.0% of patients were White. The V30M variant was most prevalent (60.1% of patients), and prevalence varied by region. Overall, 56.5% and 17.3% of patients had received previous treatment with tafamidis or diflunisal, respectively. A majority of patients (79.2%) had Coutinho stage 1 disease (unimpaired ambulation) and early (before age 50) disease onset (53.0%). Time from diagnosis to enrollment was 46.6 (57.4) months (mean [standard deviation]). Most patients had a baseline polyneuropathy disability (PND) score of I (40.5%) or II (41.1%), and the mean modified Neuropathy Impairment Score + 7 (mNIS + 7) was 79.0. Conclusion: The recruited population in the ongoing NEURO-TTRansform study has global representation characteristic of contemporary clinical practice. Trial Registration: ClinicalTrials.gov identifier NCT04136184.
KW - ATTR
KW - Amyloid
KW - Cardiomyopathy
KW - Eplontersen
KW - Polyneuropathy
KW - Transthyretin amyloidosis
UR - http://www.scopus.com/inward/record.url?scp=85144143659&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85144143659&partnerID=8YFLogxK
U2 - 10.1007/s40120-022-00414-z
DO - 10.1007/s40120-022-00414-z
M3 - Article
AN - SCOPUS:85144143659
VL - 12
SP - 267
EP - 287
JO - Neurology and Therapy
JF - Neurology and Therapy
SN - 2193-8253
IS - 1
ER -