Quality of life outcomes in APOLLO, the phase 3 trial of the RNAi therapeutic patisiran in patients with hereditary transthyretin-mediated amyloidosis

Amyloid. 2020 Sep;27(3):153-162. doi: 10.1080/13506129.2020.1730790. Epub 2020 Mar 4.

Abstract

Introduction: Hereditary transthyretin-mediated (hATTR) amyloidosis is a rare, fatal, multisystem disease leading to deteriorating quality of life (QOL). The impact of patisiran on QOL in patients with hATTR amyloidosis with polyneuropathy from the phase 3 APOLLO study (NCT01960348) is evaluated.Methods: Patients received either patisiran 0.3 mg/kg (n = 148) or placebo (n = 77) intravenously once every three weeks for 18 months. Multiple measures were used to assess varying aspects of QOL.Results: At 18 months, compared with placebo, patisiran improved Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) score; (least squares [LS] mean difference: -21.1; p = 1.10 × 10-10; improved across all domains), EuroQoL 5-dimensions 5-levels (LS mean difference: 0.2; p = 1.4 × 10-12), EuroQoL-visual analog scale (LS mean difference: 9.5; p=.0004), Rasch-built Overall Disability Scale (LS mean difference: 9.0; p = 4.07 × 10-16) and Composite Autonomic Symptom Score-31(COMPASS-31; LS mean difference: -7.5; p=.0008). Placebo-treated patients experienced rapid QOL deterioration; treatment effects for patisiran were observed as early as 9 months. At 18 months, patisiran improved Norfolk QOL-DN total score and three individual domains as well as COMPASS-31 total scores relative to baseline. Consistent benefits were also observed in the cardiac subpopulation.Conclusion: The benefits of patisiran across all QOL measures and the rapid deterioration observed with placebo, highlight the urgency in early treatment for patients with hATTR amyloidosis with polyneuropathy.

Keywords: APOLLO; Norfolk QOL-DN; hereditary transthyretin-mediated amyloidosis; patisiran; quality of life.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Amyloid Neuropathies, Familial / complications
  • Amyloid Neuropathies, Familial / drug therapy*
  • Amyloid Neuropathies, Familial / genetics
  • Amyloid Neuropathies, Familial / pathology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mutation / drug effects
  • Placebo Effect
  • Polyneuropathies / complications
  • Polyneuropathies / drug therapy*
  • Polyneuropathies / genetics
  • Polyneuropathies / pathology
  • Prealbumin / genetics*
  • Quality of Life
  • RNA, Small Interfering / administration & dosage*
  • Young Adult

Substances

  • Prealbumin
  • RNA, Small Interfering
  • TTR protein, human
  • patisiran

Supplementary concepts

  • Amyloidosis, Hereditary, Transthyretin-Related