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Efficacy and safety of vutrisiran for patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: a randomized clinical trial

Adams, David; Tournev, Ivailo L; Taylor, Mark S; Coelho, Teresa; Planté-Bordeneuve, Violaine; Berk, John L; González-Duarte, Alejandra; ... Polydefkis, Michael; + view all (2022) Efficacy and safety of vutrisiran for patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: a randomized clinical trial. Amyloid 10.1080/13506129.2022.2091985. (In press). Green open access

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Abstract

BACKGROUND: The study objective was to assess the effect of vutrisiran, an RNA interference therapeutic that reduces transthyretin (TTR) production, in patients with hereditary transthyretin (ATTRv) amyloidosis with polyneuropathy. METHODS: HELIOS-A was a phase 3, global, open-label study comparing the efficacy and safety of vutrisiran with an external placebo group (APOLLO study). Patients were randomized 3:1 to subcutaneous vutrisiran 25 mg every 3 months (Q3M) or intravenous patisiran 0.3 mg/kg every 3 weeks (Q3W) for 18 months. RESULTS: HELIOS-A enrolled 164 patients (vutrisiran, n = 122; patisiran reference group, n = 42); external placebo, n = 77. Vutrisiran met the primary endpoint of change from baseline in modified Neuropathy Impairment Score +7 (mNIS+7) at 9 months (p = 3.54 × 10−12), and all secondary efficacy endpoints; significant improvements versus external placebo were observed in Norfolk Quality of Life-Diabetic Neuropathy, 10-meter walk test (both at 9 and 18 months), mNIS+7, modified body-mass index, and Rasch-built Overall Disability Scale (all at 18 months). TTR reduction with vutrisiran Q3M was non-inferior to within-study patisiran Q3W. Most adverse events were mild or moderate in severity, and consistent with ATTRv amyloidosis natural history. There were no drug-related discontinuations or deaths. CONCLUSIONS: Vutrisiran significantly improved multiple disease-relevant outcomes for ATTRv amyloidosis versus external placebo, with an acceptable safety profile.

Type: Article
Title: Efficacy and safety of vutrisiran for patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: a randomized clinical trial
Open access status: An open access version is available from UCL Discovery
DOI: 10.1080/13506129.2022.2091985
Publisher version: https://doi.org/10.1080/13506129.2022.2091985
Language: English
Additional information: © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.
Keywords: ATTRv amyloidosis; hATTR amyloidosis; patisiran; RNA interference; vutrisiran
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10152616
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