OBJECTIVES: Hereditary transthyretin amyloidosis (hATTR) is a rare, systemic, progressive, and fatal condition in which misfolded proteins, produced in the liver, deposit in muscle and organ tissue leading to symptoms of peripheral neuropathy, and possible cardiomyopathy and autonomic neuropathy. Analyses examined the impact of an investigational therapy, inotersen, versus placebo on condition-specific quality of life (QOL), as captured by the Norfolk QOL – Diabetic Neuropathy (Norfolk QOL-DN) questionnaire, in hATTR patients.

METHODS: Data come from the NEURO-TTR trial of inotersen, a multicenter, multinational, double-blind trial (NCT01737398) of 172 adults with hATTR. The Norfolk QOL-DN, a co-primary endpoint that was administered at baseline, week 35, and week 66 produces a total score and five subscale scores capturing symptoms associated with nerve damage: physical functioning (PF)/large fiber neuropathy, activities of daily living (ADL), symptoms, small fiber neuropathy, and autonomic neuropathy. Treatment impacts on mean Norfolk QOL-DN scores were tested using mixed-effects models for repeated measures (MMRM). Responder analysis compared the percentage of patients whose scores got better (i.e., decreased by at least one-half standard deviation [SD]), got worse (i.e., increased by at least one-half SD), or stayed the same using Fisher’s exact tests.

RESULTS: At week 66, MMRM showed significant treatment effects supporting inotersen over placebo for most Norfolk QOL-DN scores, with better changes in mean scores on the ADL, PF/large fiber, and symptoms subscales, and total score, all p<0.01. Responder analysis indicated that the percentages of patients whose scores were the same or meaningfully improved from baseline to week 66 was significantly higher for those on inotersen than for placebo for the total score (81% vs. 56%), ADL (81% vs. 52%), PF/large fiber (80% vs. 58%), and symptoms subscale scores (84% vs. 65%), all p<0.02.

CONCLUSIONS: Inotersen exhibited positive treatment effects on condition-specific QOL, providing evidence of efficacy for hATTR patients.