Open Label Extension of the Phase 3 Study NEURO-TTR to Assess the Long-term Efficacy and Safety of Inotersen in Patients With Hereditary Transthyretin Amyloidosis (P1.324)

Objective: To report long-term efficacy and safety of inotersen, an antisense oligonucleotide inhibitor of transthyretin protein production, in the Phase 3 open-label extension (OLE) study (NCT02175004). Background: Hereditary transthyretin amyloidosis with (hATTR) is a severe, progressive, disabling, fatal disease caused by systemic deposition of amyloid, eventually leading to multiorgan failure. Design/Methods: Patients with hATTR who completed the phase 3 NEURO-TTR study were eligible to receive inotersen (300-mg weekly subcutaneous doses) up to 5 years in this OLE. The OLE monitored for adverse events and change from baseline in the Norfolk Quality of Life—Diabetic Neuropathy (Norfolk QOL-DN) score (136 points total, high scores indicate worse QOL) and modified neuropathy impairment score +7 (mNIS+7) (346 points total, high scores indicate worse neuropathy). Results: At the time of the interim analysis, 114 patients had enrolled in the OLE. Most of the patients were white (95%) and male (70%), and, at OLE baseline, mean age was 61.4 years, and 69% had cardiomyopathy. Mean disease duration from time of symptom onset to OLE baseline was 81.8 months. Mean OLE baseline mNIS+7 composite scores and Norfolk QOL-DN total scores were 92.0 and 55.2, respectively. One-year OLE follow-up results will be presented. Conclusions: Results of the OLE showed continued benefit as measured by Norfolk QOL-DN and mNIS+7, and a safety profile similar to that observed in the placebo-controlled study. Study Supported by: Ionis Pharmaceuticals Disclosure: 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. 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. 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. 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. Whelan has nothing to disclose. Dr. Merlini 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. Gorevic has received personal compensation in an editorial capacity for Amyloid. Dr. Gorevic has received research support from Ionis, Alnylam, Pfizer. 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. Benson has received research support from Ionis. Dr. Gertz has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ionis, Alnylam, Prothena.