P011. Impact of Patisiran on Activities of Daily Living and Functional Status in hATTR Amyloidosis

Abstract

<h3>Background</h3> Hereditary transthyretin-mediated (hATTR) amyloidosis, a rare, multi-systemic, life-threatening disease, causes neurologic and cardiac dysfunction, leading to impaired functional status and declining ability to perform activities of daily living (ADLs). <h3>Objectives</h3> To analyze the impact of patisiran on ADLs and functional status in the Phase 3 APOLLO study. <h3>Methods</h3> APOLLO was a randomized, placebo-controlled study of patisiran in patients with hATTR amyloidosis with polyneuropathy (NCT01960348). ADL/functional status assessments included: Rasch-built Overall Disability Scale (R-ODS), Karnofsky Performance Status (KPS), the ADL subdomain of Norfolk QOL-DN (Norfolk ADL). Post-hoc analyses quantified patients with no change/improvement in these assessments at 18 months. <h3>Results</h3> APOLLO enrolled 225 patients worldwide with a mean age of 60.5 years, 74% male, and 43% with V30M transthyretin mutation. At baseline, patisiran and placebo groups had similar R-ODS, KPS, and Norfolk ADL scores. After 18 months, a higher proportion of patisiran-treated patients experienced no change/improvement in functional status and ADLs relative to placebo: R-ODS 49.3% vs 13.0% (odds ratio [OR] 6.5, 95% confidence interval [CI] 2.8 to 15.4), KPS 64.9% vs 42.9%, (OR 2.5, 95% CI 1.3 to 4.8), Norfolk ADL 56.2% vs 20.4% (OR 5.0, 95% CI 2.4 to 10.5). <h3>Conclusions</h3> In APOLLO, the largest randomized clinical study of patients with hATTR amyloidosis with polyneuropathy to date, patisiran preserved ability to perform ADLs and functional status for the majority of patients and demonstrated greater odds of stabilizing or improving these assessments compared to placebo.