Tafamidis reduces disease progression in patients with transthyretin familial amyloid polyneuropathy: supportive post-hoc analyses of a pivotal trial

Background Safety and efficacy of once-daily 20 mg tafamidis, a transthyretin (TTR) stabilizer, was evaluated in an 18-month, multicentre, randomized, double-blind, placebo-controlled study in 128 patients with early symptomatic V30M TTR familial amyloid polyneuropathy (TTR-FAP). In the intent-to-treat population, a responder analysis for Neuropathy Impairment Score-Lower Limb (NIS-LL) (co-primary with Norfolk Quality of Life-Diabetic Neuropathy) favoured tafamidis (P=0.07). A pre-specified, key secondary analysis of change from baseline to Month 18 in NIS-LL continuous scores was significant (P=0.04). Placebo-corrected point estimates for 5 pre-specified and validated measures of disease progression also favoured tafamidis and were directionally consistent. Additional post-hoc analyses supporting tafamidis for delaying progression of TTR-FAP are reported here.