TY - JOUR
T1 - Efficacy and safety of vutrisiran for patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy
T2 - a randomized clinical trial
AU - The HELIOS-A Collaborators
AU - Adams, David
AU - Tournev, Ivailo L.
AU - Taylor, Mark S.
AU - Coelho, Teresa
AU - Planté-Bordeneuve, Violaine
AU - Berk, John L.
AU - González-Duarte, Alejandra
AU - Gillmore, Julian D.
AU - Low, Soon Chai
AU - Sekijima, Yoshiki
AU - Obici, Laura
AU - Chen, Chongshu
AU - Badri, Prajakta
AU - Arum, Seth M.
AU - Vest, John
AU - Polydefkis, Michael
AU - Drost, Gea
N1 - Publisher Copyright:
© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
PY - 2023
Y1 - 2023
N2 - 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.ClinicalTrials.gov: NCT03759379.
AB - 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.ClinicalTrials.gov: NCT03759379.
KW - ATTRv amyloidosis
KW - hATTR amyloidosis
KW - patisiran
KW - RNA interference
KW - vutrisiran
UR - http://www.scopus.com/inward/record.url?scp=85134730413&partnerID=8YFLogxK
U2 - 10.1080/13506129.2022.2091985
DO - 10.1080/13506129.2022.2091985
M3 - Article
C2 - 35875890
AN - SCOPUS:85134730413
SN - 1350-6129
VL - 30
SP - 18
EP - 26
JO - Amyloid
JF - Amyloid
IS - 1
ER -