Baseline characteristics of patients with hereditary transthyretin (hATTR) amyloidosis with polyneuropathy enrolled in the phase 3 study NEURO-TTR demonstrate significant disease burden

Background and aims: hATTR is a rare, progressive, and fatal disease, caused by systemic accumulation of transthyretin (TTR) protein that significantly impacts patient quality of life (QOL). We evaluated QOL at baseline in patients with hATTR with polyneuropathy (hATTR-PN) in the NEURO-TTR study (NCT01737398). Methods: Adults (n=172) with hATTR-PN (stage 1 or 2) were randomized (2:1) and received 300-mg weekly subcutaneous inotersen, an antisense oligonucleotide inhibitor of TTR protein production, or placebo. At baseline, neuropathy was assessed using the modified Neuropathy Impairment Score+7 (mNIS+7), and QOL was assessed using the patient-reported questionnaires Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) and the SF-36v2 Health Survey (SF-36v2). For these analyses, baseline QOL scores from patients in this study were reported relative to healthy controls. Results: At baseline, 69% of patients were male; 67.4% stage 1 and 32.6% stage 2 disease; and 63% of patients had cardiomyopathy. Mean baseline QOL scores were significantly worse for patients with hATTR than healthy controls. The baseline mean (standard deviation [SD]) scores in QOL measures for patients with hATTR vs healthy controls was 48.4 (27.2) vs 2.6 (5.0) for Norfolk QOL-DN total score (higher scores reflect worse QOL) and 36.3 (9.1) vs 50.0 for SF-36v2 Physical Component Summary score (lower scores reflect worse QOL). The mNIS+7 and Norfolk QOL-DN total score showed strong correlation with each other and with disease severity. Conclusion: The significantly impaired QOL observed in patients with hATTR compared with healthy controls confirms the unmet medical need for effective treatments that can reduce disease burden.