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Impact of Baseline Neuropathy Severity on Vutrisiran Treatment Response in the Phase 3 HELIOS-A Study.
Luigetti, Marco; Quan, Dianna; Berk, John L; Conceição, Isabel; Misumi, Yohei; Chao, Chi-Chao; Bender, Shaun; Aldinc, Emre; Vest, John; Adams, David.
Afiliación
  • Luigetti M; Dipartimento di Neuroscienze, Organi di Senso e Torace, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo Agostino Gemelli, 8, 00168, Rome, Italy. mluigetti@gmail.com.
  • Quan D; Dipartimento di Neuroscienze, Università Cattolica del Sacro Cuore, Rome, Italy. mluigetti@gmail.com.
  • Berk JL; Department of Neurology, University of Colorado Anschutz, Aurora, CO, USA.
  • Conceição I; Boston Medical Center, Boston, MA, USA.
  • Misumi Y; Department of Neurology, CHULN, Hospital Santa Maria and Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
  • Chao CC; Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
  • Bender S; Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan.
  • Aldinc E; Alnylam Pharmaceuticals, Cambridge, MA, USA.
  • Vest J; Alnylam Pharmaceuticals, Cambridge, MA, USA.
  • Adams D; Alnylam Pharmaceuticals, Cambridge, MA, USA.
Neurol Ther ; 13(3): 625-639, 2024 Jun.
Article en En | MEDLINE | ID: mdl-38512694
ABSTRACT

INTRODUCTION:

Hereditary transthyretin (ATTRv, v for variant) amyloidosis is a rare, progressive, fatal disease with multisystem manifestations, caused by pathogenic variants in the transthyretin (TTR) gene. Vutrisiran, an RNA interference therapeutic that results in rapid TTR knockdown, improved neuropathy and quality of life (QOL) versus external placebo in patients with ATTRv amyloidosis with polyneuropathy in the phase 3 HELIOS-A study (NCT03759379). This post hoc analysis evaluates the impact of baseline neuropathy severity on response to vutrisiran treatment.

METHODS:

Patients were randomized (31) to vutrisiran (n = 122; 25 mg subcutaneous injection once every 3 months) or patisiran (n = 42; 0.3 mg/kg intravenous infusion once every 3 weeks), which served as a reference group. In this post hoc analysis, patients were grouped into quartiles of increasing baseline Neuropathy Impairment Score (NIS) Quartile (Q)1 ≥ 5.0 to ≤ 20.5; Q2 > 20.5 to ≤ 44.1; Q3 > 44.1 to ≤ 73.1; Q4 > 73.1 to ≤ 127.0. Mean change from baseline to Month 18 was summarized by quartile for a range of efficacy endpoints.

RESULTS:

Across all baseline NIS quartiles, vutrisiran demonstrated benefit versus external placebo in measures of neuropathy severity (modified NIS + 7), QOL (Norfolk Quality of Life-Diabetic Neuropathy), disability (Rasch-built Overall Disability Scale), gait speed (10-m walk test), and nutritional status (modified body mass index). Overall, patients in lower versus higher NIS quartiles (less severe neuropathy) at baseline maintained better scores at Month 18. The external placebo group progressively worsened in all measures at Month 18.

CONCLUSIONS:

Vutrisiran demonstrated benefit in neurologic function and other key efficacy measures versus external placebo across all four baseline neuropathy severity quartiles. Patients initiating vutrisiran earlier in their disease course retained the highest neurologic function level after 18 months, highlighting the importance of early diagnosis and treatment. TRIAL REGISTRATION NUMBER ClinicalTrials.gov NCT03759379.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Neurol Ther Año: 2024 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Nueva Zelanda
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Neurol Ther Año: 2024 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Nueva Zelanda