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

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. Patients received either patisiran 0.3 mg/kg ( = 148) or placebo ( = 77) intravenously once every three weeks for 18 months. Multiple measures were used to assess varying aspects of QOL. 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;  = 1.10 × 10; improved across all domains), EuroQoL 5-dimensions 5-levels (LS mean difference: 0.2;  = 1.4 × 10), EuroQoL-visual analog scale (LS mean difference: 9.5; =.0004), Rasch-built Overall Disability Scale (LS mean difference: 9.0;  = 4.07 × 10) and Composite Autonomic Symptom Score-31(COMPASS-31; LS mean difference: -7.5; =.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. 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.