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Long-term efficacy and safety of vutrisiran in hereditary transthyretin amyloidosis with polyneuropathy: final analysis of the HELIOS-A randomized treatment extension

Publication Details

Amyloid

June 2026

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Author(s)

Cécile Cauquil¹, David Adams¹, Julian Gillmore², Alejandra Gonzalez-Duarte³ ⁴, Michelle Mezei⁵, Laura Obici⁶, Yoshiki Sekijima⁷, Weizhi Zhao⁸, Katherine Boyle⁸, Prajakta Badri⁸, Marianne Sweetser⁸, Colleen Moffitt⁸, Márcia Waddington-Cruz⁹ ¹⁰

Affiliations

¹Neurology Department, CHU Bicêtre, APHP, Université Paris-Saclay, Le Kremlin Bicêtre Cedex, France; ²National Amyloidosis Centre, University College London, Royal Free Hospital, London, UK; ³Instituto Nacional de Ciencias Médicas y Nutriciόn Salvador Zubirán, Mexico, Mexico; ⁴Neurology Department, Dysautonomia Center, NYU Grossman School of Medicine, New York, NY, USA; ⁵Division of Neurology, Vancouver General Hospital, University of British Columbia, Vancouver, Canada; ⁶Amyloidosis Research and Treatment Centre, IRCCS Fondazione Policlinico San Matteo, Pavia, Italy; ⁷Department of Medicine (Neurology & Rheumatology), Shinshu University School of Medicine, Matsumoto, Japan; ⁸Alnylam Pharmaceuticals, Cambridge, MA, USA; ⁹Amyloidosis Center, CEPARM, University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; ¹⁰Amyloidosis Center, Américas-Samaritano-Vitória Barra Hospital Complex, Rio de Janeiro, Brazil

Abstract

Background:

The long-term efficacy and safety of vutrisiran in hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) were assessed in the HELIOS-A randomized treatment extension (RTE).

Methods:

Patients who completed the 18-month, phase 3, open-label HELIOS-A study could enter an open-label RTE with re-randomization 1:1 to vutrisiran 25 mg every 3 months (Q3M) or 50 mg every 6 months (Q6M; transitioned to 25 mg Q3M following an amendment) for up to 42 months (RTE M18 efficacy assessment; RTE M42 safety and transthyretin (TTR) levels).

Results:

In the RTE, 149 patients were re-randomized to vutrisiran (25 mg Q3M [n = 76]; 50 mg Q6M [n = 73]). Mean serum TTR reduction from study baseline at RTE M42 for the total vutrisiran group was 84.5%. Efficacy was sustained from RTE baseline through RTE M18 in modified Neuropathy Impairment Score +7, Norfolk Quality of Life-Diabetic Neuropathy score, 10-meter walk test, Rasch-built Overall Disability Scale and modified body mass index (mBMI); most patients (67.8%) had stable polyneuropathy disability scores. Most AEs were mild/moderate in severity with no new safety concerns.

Conclusions:

Results from the HELIOS-A RTE demonstrate relative stability with only modest changes in disease activity, sustained serum TTR reductions, and an acceptable safety profile with long-term vutrisiran treatment in patients with ATTRv-PN.

ClinicalTrials.gov: NCT03759379.