source: Amyloid: The Official Journal of the International Society of Amyloidosis

year: 2022

authors: David Adams, Ivailo L. Tournev, Mark S. Taylor, Teresa Coelho, Violaine Planté-Bordeneuve, John L. Berk, Alejandra González-Duarte, Julian D. Gillmore, Soon-Chai Low, Yoshiki Sekijima, Laura Obici, Chongshu Chen, Prajakta Badri, Seth M. Arum, John Vest, Michael Polydefkis

summary/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.

organization: Université Paris-Saclay, France; University Hospital Aleksandrovska, Bulgaria; New Bulgarian University, Bulgaria; Westmead Hospital and Westmead Clinical School, University of Sydney, Australia; Centro Hospitalar Universitário do Porto, Portugal; University Paris Est - Créteil, France; Boston University, USA; Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México; National Amyloidosis Centre, University College London, UK; University Malaya Medical Centre, Malaysia; Shinshu University School of Medicine, Japan; Amyloidosis Research and Treatment Centre, IRCCS Fondazione Policlinico San Matteo, Italy; Alnylam Pharmaceuticals, USA; Johns Hopkins University School of Medicine, USA

DOI: 10.1080/13506129.2022.2091985

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