Burden of Hereditary Transthyretin Amyloidosis With Polyneuropathy in Patients Enrolled in the Phase 3 Study NEURO-TTR (P1.331)

Objective: To report the quality of life (QOL) of patients with hereditary transthyretin (TTR) amyloidosis (hATTR) enrolled in the global, randomized, double-blind, placebo-controlled phase 3 study NEURO-TTR (NCT01737398). Background: hATTR is a severe systemic disease characterized by motor and sensory neuropathy, autonomic neuropathy, nephropathy, and cardiomyopathy, which severely impact activities of daily living and QOL. Design/Methods: Patients (172) with hATTR-PN ≥18 years of age were treated after randomization (2:1) to receive 300-mg weekly subcutaneous doses of inotersen, an antisense oligonucleotide inhibitor of TTR protein production, or placebo. At baseline, the modified Neuropathy Impairment Score+7 (mNIS+7) assessed neuropathy, and QOL was assessed using patient-reported questionnaires: the Norfolk Quality of Life–Diabetic Neuropathy (Norfolk QOL–DN) and the SF-36v2 ® Health Survey (SF-36v2). QOL scores were reported relative to general population (GP) normative data. For these analyses, baseline QOL scores from patients in this study were reported relative to general population (GP) normative data. Results: Most patients were white (91.9%) and male (68.6%) with a mean age of 59.2 years. 67.4% of patients had stage I and 32.6% had stage II disease. 63% had cardiomyopathy. Mean baseline QOL scores were significantly worse than the GP norms for both measures. The baseline mean Norfolk QOL-DN score was 48.4 ± 27.2 (standard deviation (SD)) compared with 2.6 ± 5.0 (SD) for the GP (higher scores reflect worse QOL). The mean SF-36v2 (Physical Component Summary [PCS]) score was 36.3 ± 9.1 (SD) compared with 50 for a GP (lower scores reflect worse QOL). There was strong correlation between severity of disease as measured by neuropathy instruments (such as mNIS+7) and patient-reported QOL measures. Conclusions: Patients with hATTR in the NEURO-TTR study have significant impairments in QOL compared with the GP, which confirms the unmet medical need for effective treatments that can reduce disease burden. Study Supported by: Ionis Pharmaceuticals Disclosure: Dr. Berk has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ionis, Alnylam. Dr. Berk has received research support from Ionis, Alnylam, Pfizer. Dr. Wang has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ionis. Dr. Wang has received research support from Ionis. Dr. Coelho has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Pfizer, Alnylam, Ionis, Prothena. Dr. Coelho has received research support from Pfizer, Ionis, Alnylam. Dr. Waddington Cruz has nothing to disclose. Dr. Polydefkis has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Pfizer, Alnylam. Dr. Dyck has nothing to disclose. Dr. Scheinberg has nothing to disclose. Dr. Plante-Bordeneuve has nothing to disclose. Dr. Barroso has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Pfizer. Dr. Barroso has received research support from Alnylam. Dr. Adams has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Pfizer, Alnylam, Prothena. Dr. Adams has received research support from Ionis, Alnylam. Dr. Brannagan has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alnylam. Dr. Brannagan has received research support from Ionis, Alnylam. Dr. Whelan has nothing to disclose. Dr. Drachman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alnylam. Dr. Drachman has received research support from Pfizer, Ionis, Alnylam. Dr. Heitner has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alnylam, Amgen, Takeda, MyoKardia. Dr. Conceicao has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Pfizer, Alnylam. Dr. Conceicao has received research support from Pfizer, Alnylam, Sanofi. Dr. Schmidt has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Pfizer, Alnylam, Ionis. Dr. Vita has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Avexis, Alnylam, Pfizer. Dr. Vita has received personal compensation in an editorial capacity for Neurological Sciences. Dr. Campistol has nothing to disclose. Dr. Gamez has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with ITALFARMACO. Dr. Gane has nothing to disclose. Dr. Gorevic has received personal compensation in an editorial capacity for Amyloid. Dr. Gorevic has received research support from Ionis, Alnylam, Pfizer. Dr. Oliveira has nothing to disclose. Dr. Monia has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ionis. Dr. hughes has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ionis. Dr. Kwoh has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ionis. Dr. McEvoy has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ionis. Dr. Baker has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ionis. Dr. Baker holds stock and/or stock options in Ionis. Dr. Ackermann has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ionis. Dr. Guthrie has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ionis. Dr. Sikora Kessler has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Optum (from Ionis). Dr. Gertz has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ionis, Alnylam, Prothena. Dr. Benson has received research support from Ionis. Dr. Merlini has nothing to disclose.