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.
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).
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.
Efficacy and safety data to be presented.
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.Le texte complet de cet article est disponible en PDF.
Mots clés : Mutations, ARNi therapeutic, Amylose héréditaire à transthyrétine