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

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.

• Authors: Laura Obici, John L Berk, Alejandra González-Duarte, Teresa Coelho, Julian Gillmore, Hartmut H-J Schmidt, Matthias Schilling, Taro Yamashita, Céline Labeyrie, Thomas H Brannagan 3rd, Senda Ajroud-Driss, Peter Gorevic, Arnt V Kristen, Jaclyn Franklin, Jihong Chen, Marianne T Sweetser, Jing Jing Wang, David Adams
• Journal: Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis (Amyloid) Vol. 27 Issue 3 Pg. 153-162 (Sep 2020) ISSN: 1744-2818 [Electronic] England
• PMID: 32131641 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

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

Topics

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