PMID- 36525140 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230223 IS - 2193-8253 (Print) IS - 2193-6536 (Electronic) IS - 2193-6536 (Linking) VI - 12 IP - 1 DP - 2023 Feb TI - Characteristics of Patients with Hereditary Transthyretin Amyloidosis-Polyneuropathy (ATTRv-PN) in NEURO-TTRansform, an Open-label Phase 3 Study of Eplontersen. PG - 267-287 LID - 10.1007/s40120-022-00414-z [doi] 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. CI - (c) 2022. The Author(s). FAU - Coelho, Teresa AU - Coelho T AD - Centro Hospitalar Universitario do Porto, Porto, Portugal. FAU - Waddington Cruz, Marcia AU - Waddington Cruz M AD - Hospital Universitario Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Chao, Chi-Chao AU - Chao CC AD - National Taiwan University Hospital, Taipei, Taiwan. FAU - Parman, Yesim AU - Parman Y AD - Istanbul Universitesi-Istanbul Tip Fakultesi, Istanbul, Turkey. FAU - Wixner, Jonas AU - Wixner J AD - Umea University, Umea, Sweden. FAU - Weiler, Markus AU - Weiler M AD - Amyloidosis Center and Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany. FAU - Barroso, Fabio A AU - Barroso FA AD - Neurology Department, Fleni, Buenos Aires, Argentina. FAU - Dasgupta, Noel R AU - Dasgupta NR AD - Indiana University School of Medicine, Indianapolis, IN, USA. FAU - Jung, Shiangtung W AU - Jung SW AD - Ionis Pharmaceuticals, Inc., Carlsbad, CA, USA. FAU - Schneider, Eugene AU - Schneider E AD - Ionis Pharmaceuticals, Inc., Carlsbad, CA, USA. FAU - Viney, Nicholas J AU - Viney NJ AD - Ionis Pharmaceuticals, Inc., Carlsbad, CA, USA. FAU - Dyck, P James B AU - Dyck PJB AD - Mayo Clinic, Rochester, MN, USA. FAU - Ando, Yukio AU - Ando Y AD - Kumamoto University, Kumamoto, Japan. FAU - Gillmore, Julian D AU - Gillmore JD AD - Centre for Amyloidosis, University College London, London, UK. FAU - Khella, Sami AU - Khella S AD - Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. FAU - Gertz, Morie A AU - Gertz MA AD - Division of Hematology, Mayo Clinic, Rochester, MN, USA. FAU - Obici, Laura AU - Obici L AD - Amyloidosis Research and Treatment Centre, IRCCS Fondazione Policlinico San Matteo, Pavia, Italy. FAU - Berk, John L AU - Berk JL AD - Amyloidosis Center, School of Medicine/Boston Medical Center, Boston University, 72 East Concord St., K503, Boston, MA, 02118, USA. jberk@bu.edu. LA - eng SI - ClinicalTrials.gov/NCT04136184 PT - Journal Article DEP - 20221216 PL - New Zealand TA - Neurol Ther JT - Neurology and therapy JID - 101637818 PMC - PMC9837340 OAB - Hereditary transthyretin amyloidosis, also called ATTRv amyloidosis, is a rare and serious disease that is passed down within families. People with ATTRv amyloidosis have a genetic variant that causes their liver to make abnormal versions of the transthyretin protein (also known as "TTR"), which clump together into "clusters" called amyloids. The amyloid clusters build up in various body tissues and organs such as the liver, nerves, heart, and kidney, causing damage that could ultimately lead to death. ATTRv amyloidosis is a progressive disease, meaning that it gets worse over time. Liver transplant has traditionally been the only treatment option. Recently, drugs that target TTR have been approved by the FDA, and potential drugs are being tested in clinical trials. Eplontersen is designed to degrade TTR mRNA in the liver and inhibit the production of TTR protein. NEURO-TTRansform is a global phase 3 study investigating the effectiveness and safety of eplontersen in 168 adults with ATTRv amyloidosis with polyneuropathy (ATTRv-PN), a disease in which amyloid accumulation in peripheral nerves causes multisystem damage and eventually death. This scientific article describes the characteristics of the patients at enrollment, including age, gender, geographic location, and disease-related information, to help improve the understanding of ATTRv-PN. NEURO-TTRansform is an ongoing study, and the results will be published at a later time as prespecified in the analysis plan. OABL- eng OTO - NOTNLM OT - ATTR OT - Amyloid OT - Cardiomyopathy OT - Eplontersen OT - Polyneuropathy OT - Transthyretin amyloidosis COIS- 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. Marcia 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. Yesim 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. EDAT- 2022/12/17 06:00 MHDA- 2022/12/17 06:01 PMCR- 2022/12/16 CRDT- 2022/12/16 11:27 PHST- 2022/08/25 00:00 [received] PHST- 2022/10/17 00:00 [accepted] PHST- 2022/12/17 06:00 [pubmed] PHST- 2022/12/17 06:01 [medline] PHST- 2022/12/16 11:27 [entrez] PHST- 2022/12/16 00:00 [pmc-release] AID - 10.1007/s40120-022-00414-z [pii] AID - 414 [pii] AID - 10.1007/s40120-022-00414-z [doi] PST - ppublish SO - Neurol Ther. 2023 Feb;12(1):267-287. doi: 10.1007/s40120-022-00414-z. Epub 2022 Dec 16.