We thank the patients who participated in this trial and their families.
Funding
This research, as well as the journal’s Rapid Service Fee and Open Access Fee, was funded by Akcea Therapeutics, a subsidiary of Ionis Pharmaceuticals Inc.
Editorial Assistance
We thank Bonita S. Basnyat of QualityMetric for copy editing and preparation of this manuscript for submission, for which QualityMetric was funded by Akcea Therapeutics, a subsidiary of Ionis Pharmaceuticals Inc.
Authorship
All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.
Author Contributions
Aaron Yarlas contributed to the study design, conducted statistical analysis, drafted the first and final drafts of the manuscript, and approved the final manuscript. Andrew Lovley contributed to the study design, conducted statistical analysis, commented on previous versions of the manuscript, and read and approved the final manuscript. Kristen McCausland contributed to the study design, commented on previous versions of the manuscript, and read and approved the final manuscript. Duncan Brown contributed to the study design, commented on previous versions of the manuscript, and read and approved the final manuscript. Montserrat Vera-Llonch contributed to the study design, commented on previous versions of the manuscript, and read and approved the final manuscript. Isabel Conceição contributed to the study design, commented on previous versions of the manuscript, and read and approved the final manuscript. Chafic Karam contributed to the study design, commented on previous versions of the manuscript, and read and approved the final manuscript. Sami Khella contributed to the study design, commented on previous versions of the manuscript, and read and approved the final manuscript. Laura Obici contributed to the study design, commented on previous versions of the manuscript, and read and approved the final manuscript. Márcia Waddington-Cruz contributed to the study design, commented on previous versions of the manuscript, and read and approved the final manuscript.
List of Principal Investigators
Principal Investigators for the NEURO-TTR open-label extension study were as follows: David Adams, MD, PhD, Paris, France. Fabio A Barroso, MD, Buenos Aires, Argentina. Merrill D Benson, MD, Indianapolis, IN, USA. John L Berk, MD, Boston, MA, USA. Thomas H Brannagan III, MD, New York, NY, USA. Josep Maria Campistol Plana, MD, Barcelona, Spain. Jose Gamez Carbonell, MD, PhD, Barcelona, Spain. Teresa Coelho, MD, Porto, Portugal. Isabel Conceição, MD, Lisbon, Portugal. Brian M Drachman, MD, Philadelphia, PA, USA. Edward Gane, MD, Auckland, New Zealand. Morie A Gertz, MD, Rochester, MN. Peter D Gorevic, MD, New York, NY. Stephen B Heitner, MD, Portland, OR. Arnt Kristen, Heidelberg, Germany. Giampaolo Merlini, MD, Pavia, Italy. Laura Obici, MD, Pavia, Italy. Violaine Plante-Bordeneuve, MD, Créteil, France. Michael Polydefkis, MD, MHS, Baltimore, MD. Fabrizio Salvi, MD, Bologna, Italy. Morton Scheinberg, MD, São Paulo, Brazil. Hartmut H Schmidt, MD, Muenster, Germany. Acary Souza Bulle Oliveira, MD, São Paulo, Brazil. Giuseppe Vita, MD, Messina, Italy. Annabel K Wang, MD, Irvine, CA. Márcia Waddington-Cruz, MD, PhD, Rio de Janeiro, Brazil. Carol Whelan, MD. London, UK.
Prior Presentation
Portions of this research were presented at the following conferences: American Academy of Neurology (AAN) Annual Meeting, April 17–22, 2020, Virtual; XVII International Symposium on Amyloidosis (ISA), September 1–18, 2020, Virtual; and American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) Annual Meeting, October 7–10, 2020, Virtual.
Disclosures
Aaron Yarlas, Andrew Lovley, and Kristen McCausland are employees of QualityMetric, which received payment from Ionis Pharmaceuticals to conduct these analyses and develop this manuscript. Duncan Brown and Montserrat Vera-Llonch are employees of and own stock in Ionis Pharmaceuticals. Isabel Conceição acknowledges financial support as a primary investigator for FoldRx Pharmaceuticals/Pfizer, Alnylam Pharmaceuticals, and IONIS Pharmaceuticals, and serves on the Transthyretin Amyloidosis Outcome Survey (THAOS) scientific advisory board. Chafic Karam has received consulting honoraria from Argenx, CSLBehring, Alnylam, Akcea Therapeutics, Biogen, and Sanofi. Sami Khella has received consulting honoraria from Ionis Pharmaceuticals, Akcea Therapeutics, Alnylam, Pfizer, and Eidos. Laura Obici has received speaker honoraria from Akcea, Pfizer, and Alnylam. Márcia Waddington-Cruz has received honoraria from NHI, Prothena, FoldRx, Akcea Therapeutics, Pfizer, Alnylam Pharmaceuticals, PTC, and Genzyme for travel expenses related to presentations at medical meetings, and for acting as a consultant and as a principal investigator in clinical trials.
Compliance with Ethics Guidelines
The trial protocol was approved by institutional review boards or local ethics committees. The trial was conducted in accordance with Good Clinical Practice guidelines of the International Conference on Harmonisation and the principles of the Declaration of Helsinki of 1964 and its later amendments. Written informed consent was obtained from all participants included in the study.
Data Availability
Data can be made available upon reasonable request.