Outcomes of patients with hereditary transthyretin-mediated amyloidosis with early onset V30M versus all other mutations in APOLLO, a Phase 3 study of patisiran

Abstract

Introduction hATTR is multi-systemic, life-threatening, caused by transthyretin gene mutations. Investigational RNAi therapeutic resulted in statistically significant improvement in neuropathy and Quality of Life measures compared to placebo in Phase 3. Objective We evaluated patisiran efficacy and safety in patients with early onset V30M versus all other mutations. Patients and methods APOLLO was a multi-center, international, randomized (2:1), double-blind study of patisiran 0.3mg/kg or placebo IV q3W in hATTR amyloidosis patients with polyneuropathy ( NCT01960348 ). Primary endpoint was changed from baseline at 18-months in mNIS + 7 with multiple secondary endpoints including Norfolk QOL-DN. Pre-specified subgroup analyses were conducted to evaluate patients with early onset V30M (≤ 50 years of age at onset) and those with all other mutations including late onset V30M (> 50 years of age at onset). Results APOLLO enrolled 225 patients with 39 different TTR mutations including 42.7% with V30M mutations with 10.2% considered to have early onset V30M disease. Similar to the overall patient population, patisiran demonstrated improvement in mNIS + 7 and Norfolk QOL-DN compared to placebo in early onset V30M and as well as in all other mutations at 18-months. Discussion Efficacy and safety data to be presented. Conclusion Patisiran, investigated in patients with early and late onset V30M as well as a wide range of non-V30M genotypes, demonstrated consistent benefit over placebo in mNIS + 7 and Norfolk QOL-DN.