Akcea Therapeutics, Inc. announced publication of long-term data from the open-label extension (OLE) of the pivotal NEURO-TTR study of TEGSEDI® (inotersen) in patients with hereditary transthyretin (hATTR) amyloidosis with polyneuropathy. The primary objective of the OLE study was to evaluate the safety and tolerability of long-term dosing with TEGSEDI. Secondary objectives of the study included understanding progression based on measures such as the modified Neuropathy Impairment Score +7 (mNIS+7) and the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN). Understanding changes over time in generic health-related quality of life based on the Short Form 36 Health Survey (SF-36) was an exploratory objective. This interim analysis, published in the European Journal of Neurology, show that treatment with TEGSEDI was not associated with additional safety concerns or signs of increased toxicity in study participants treated for up to five years. Treatment with TEGSEDI resulted in continued efficacy in patients after two years. Results also showed that patients who started treatment with TEGSEDI earlier (received TEGSEDI treatment in the NEURO-TTR study) achieved greater long-term disease stabilization compared to those who switched from placebo to TEGSEDI in the OLE study. hATTR amyloidosis is an under-recognized, debilitating and progressive disease that is caused by the buildup of TTR proteins that misfold due to inherited mutations. It is characterized by the deposition of amyloid fibrils throughout the body including in nervous tissue and can have a devastating impact on patients’ quality of life. TEGSEDI is a once-weekly, at-home subcutaneous injection that targets the polyneuropathy of hATTR amyloidosis at its source by reducing production of the TTR protein. Results from the pivotal, randomized, double-blind, placebo-controlled NEURO-TTR study demonstrated that hATTR amyloidosis patients treated with TEGSEDI experienced significant benefit compared to patients treated with placebo across both co-primary endpoints: mNIS+7, a measure of neuropathic disease progression and the Norfolk QoL-DN. At the end of the study, participants were given the opportunity to enroll in the OLE study and continue treatment with TEGSEDI or switch from placebo. Of the 139 patients who completed the NEURO-TTR study 135 participants (97%) continued in the OLE study. Among those who participated in the ongoing OLE study, 85 continued to receive TEGSEDI and 50 switched from placebo to TEGSEDI. No new safety concerns were identified in patients treated with TEGSEDI in the OLE study. There was also no evidence of increased risk for grade 4 thrombocytopenia or acute glomerulonephritis with increased duration of exposure to TEGSEDI. Regular, required platelet and renal monitoring proved to be effective in managing patients’ risk. The most common (>10%) adverse events (AEs) include nausea, urinary tract infection, vomiting, diarrhea, fatigue, peripheral edema, injection site pain and thrombocytopenia. Overall, 19 (14.1%) patients discontinued TEGSEDI due to treatment-emergent adverse events (TEAEs). Nine (6.7%) patients died during the OLE study but none of the deaths were considered related to TEGSEDI. Patients administered TEGSEDI throughout the NEURO-TTR and OLE studies experienced substantial reductions in TTR protein levels (77% reduction on average) compared to their baseline from the NEURO-TTR study. In addition, those treated with TEGSEDI for 39 cumulative months in the NEURO-TTR and OLE studies showed sustained benefit compared to the predicted worsening with placebo. Likewise, those patients who switched from placebo to TEGSEDI demonstrated sustained improvement of neurologic disease progression and quality of life as measured by the mNIS+7, the Norfolk QoL-DN, and the SF-36 Physical Component Summary score (PCS) compared with a continued predicted worsening with placebo. Finally, patients treated earlier with TEGSEDI achieved greater benefit in mNIS+7 (17.06 points) and Norfolk QoL-DN (11.89 points) compared to patients who switched from placebo to TEGSEDI in the OLE study, highlighting the importance of early commencement of TEGSEDI in appropriate patients.