TY - JOUR
T1 - Inotersen for the treatment of adults with polyneuropathy caused by hereditary transthyretin-mediated amyloidosis
AU - Gertz, Morie A.
AU - Scheinberg, Morton
AU - Waddington-Cruz, Márcia
AU - Heitner, Stephen B.
AU - Karam, Chafic
AU - Drachman, Brian
AU - Khella, Sami
AU - Whelan, Carol
AU - Obici, Laura
N1 - Funding Information:
MA Gertz reports personal fees from Ionis/Akcea, Alnylam, Prothena, Celgene, Janssen, Spectrum, Annexon, Appellis, Amgen, Medscape, Physicians Education Resource, Abbvie (Data Safety Monitoring board), Research to Practice; speaker fees from Teva, Johnson and Johnson, Medscape, DAVA oncology; Advisory Boards for Pharmacyclics and Proclara; Royalties from Springer Publishing; and Grant Funding from Amyloidosis Foundation, International Waldenstrom Foundation, and Spectrum. M Scheinberg has been a consultant and speaker for Pfizer, GSK, Janssen, Roche, Samsung Bioepis, Boehringer Ingelheim, and Novartis. M Waddington-Cruz received honoraria from NHI, Prothena, FoldRx, Ionis, Pfizer, Alnylam, PTC, and Genzyme for travel expenses related to presentations at medical meetings, for acting as a principal investigator in clinical trials and as a consultant member. SB Heitner reports research grants from Pfizer, Eidos, and Ionis and has received consulting fees from Pfizer and Alnylam, Ionis, and Eidos. C Karam has served as a paid consultant for Akcea, Alnylam, Alexion, Biogen, CSL Behring, Cytokinetics, and Genzyme. B Drachman has served on an advisory board for Alnylam Pharmaceuticals; as a study investigator for Ionis Pharmaceuticals, Inc, Alnylam Pharmaceuticals, and Pfizer. S Khella has received honoraria from Akcea Therapeutics and Alnylam Pharmaceuticals. C Whelan has received honoraria from Akcea and Alnylam. L Obici has received speaker fees and participated on scientific advisory boards for Alnylam Pharmaceuticals, Akcea, and Pfizer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Funding Information:
Editorial assistance in the preparation of this manuscript was provided by ApotheCom (San Francisco, CA, USA) and was funded by Akcea Therapeutics (Boston, MA, USA). The funding source had no role in determining the content of the review.
Publisher Copyright:
© 2019, © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
PY - 2019/8/3
Y1 - 2019/8/3
N2 - Introduction: Hereditary transthyretin-mediated amyloidosis (ATTRv; v for variant) is an underdiagnosed, progressive, and fatal multisystemic disease with a heterogenous clinical phenotype that is caused by TTR gene mutations that destabilize the TTR protein, resulting in its misfolding, aggregation, and deposition in tissues throughout the body. Areas covered: Inotersen, an antisense oligonucleotide inhibitor, was recently approved in the United States and Europe for the treatment of the polyneuropathy of ATTRv based on the positive results obtained in the pivotal phase 3 trial, NEURO-TTR. This review will discuss the mechanism of action of inotersen and its pharmacology, clinical efficacy, and safety and tolerability. A PubMed search using the terms ‘inotersen,’ ‘AG10,’ ‘antisense oligonucleotide,’ ‘hereditary transthyretin amyloidosis,’ ‘familial amyloid polyneuropathy,’ and ‘familial amyloid cardiomyopathy’ was performed, and the results were screened for the most relevant English language publications. The bibliographies of all retrieved articles were manually searched to identify additional studies of relevance. Expert opinion: Inotersen targets the disease-forming protein, TTR, and has been shown to improve quality of life and neuropathy progression in patients with stage 1 or 2 ATTRv with polyneuropathy. Inotersen is well tolerated, with a manageable safety profile through regular monitoring for the development of glomerulonephritis or thrombocytopenia.
AB - Introduction: Hereditary transthyretin-mediated amyloidosis (ATTRv; v for variant) is an underdiagnosed, progressive, and fatal multisystemic disease with a heterogenous clinical phenotype that is caused by TTR gene mutations that destabilize the TTR protein, resulting in its misfolding, aggregation, and deposition in tissues throughout the body. Areas covered: Inotersen, an antisense oligonucleotide inhibitor, was recently approved in the United States and Europe for the treatment of the polyneuropathy of ATTRv based on the positive results obtained in the pivotal phase 3 trial, NEURO-TTR. This review will discuss the mechanism of action of inotersen and its pharmacology, clinical efficacy, and safety and tolerability. A PubMed search using the terms ‘inotersen,’ ‘AG10,’ ‘antisense oligonucleotide,’ ‘hereditary transthyretin amyloidosis,’ ‘familial amyloid polyneuropathy,’ and ‘familial amyloid cardiomyopathy’ was performed, and the results were screened for the most relevant English language publications. The bibliographies of all retrieved articles were manually searched to identify additional studies of relevance. Expert opinion: Inotersen targets the disease-forming protein, TTR, and has been shown to improve quality of life and neuropathy progression in patients with stage 1 or 2 ATTRv with polyneuropathy. Inotersen is well tolerated, with a manageable safety profile through regular monitoring for the development of glomerulonephritis or thrombocytopenia.
KW - Hereditary transthyretin-mediated amyloidosis
KW - cardiomyopathy
KW - inotersen
KW - peripheral neuropathy
KW - ribonucleic acid interference
KW - transthyretin
UR - http://www.scopus.com/inward/record.url?scp=85068527064&partnerID=8YFLogxK
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U2 - 10.1080/17512433.2019.1635008
DO - 10.1080/17512433.2019.1635008
M3 - Article
C2 - 31268366
AN - SCOPUS:85068527064
VL - 12
SP - 701
EP - 711
JO - Expert Review of Clinical Pharmacology
JF - Expert Review of Clinical Pharmacology
SN - 1751-2433
IS - 8
ER -