Long-term safety and efficacy of patisiran for hereditary transthyretin-mediated amyloidosis with polyneuropathy: 12-month results of an open-label extension study

Abstract

Background Hereditary transthyretin (ATTRv) amyloidosis is a rare, inherited, progressive disease caused by mutations in the transthyretin (TTR) gene. We aimed to assess the efficacy and safety of long-term treatment with patisiran, an RNA interference therapeutic that inhibits TTR production, in patients with ATTRv amyloidosis with polyneuropathy. MethodsThis multi-country, multi-centre, open-label extension (OLE) trial enrolled patients at 43 sites in 19 countries as of 24 September 2018. Patients were eligible if they had completed the phase 3 APOLLO (randomised, double-blind, placebo-controlled [2:1], 18-month study) or phase 2 OLE (single-arm, 24-month study) parent studies and tolerated the study drug. Eligible patients from APOLLO (APOLLO-patisiran [received patisiran during APOLLO] and APOLLO-placebo [received placebo during APOLLO] groups) and the phase 2 OLE (phase 2 OLE patisiran group) studies enrolled in this Global OLE trial and receive patisiran 0•3 mg/kg by intravenous infusion every 3 weeks for up to 5 years. Efficacy assessments include measures of polyneuropathy (modified Neuropathy Impairment Score +7 [mNIS+7]), quality of life, autonomic symptoms, nutritional status, disability, ambulation status, motor function, and cardiac stress. Patients included in the current efficacy analyses are those who had completed 12-month efficacy assessments as of the data cut-off. Safety analyses included all patients who received ≥1 dose of patisiran up to the data cut-off. The Global OLE is ongoing with no new enrolment, and current findings are based on the 12-month interim analysis. The study is registered with ClinicalTrials.gov, NCT02510261.

Use of Drugs for ATTRv Amyloidosis in the Real World: How Therapy Is Changing Survival in a Non-Endemic Area

“…Almost exclusively non-Met30 patients composed our cohort, therefore in some cases we preferred to shift patients to the new oligonucleotide drugs that have been shown to be unmistakably effective even in this population. Overall, both drugs, and particularly patisiran, have demonstrated better efficacy compared to tafamidis [ 27 , 28 , 44 , 45 , 46 ]. Despite this, in 17 of 44 patients, tafamidis was still used based on the abovementioned advantages.…”

Multidisciplinary Approaches for Transthyretin Amyloidosis

“…Subsequent reports of open-label extension studies demonstrated that patisiran maintained efficacy with an acceptable safety profile in ATTRv amyloidosis patients with polyneuropathy for up to 30 months [117,118].…”

Transthyretin Amyloidosis Therapies: Guiding the Future

“…Patisiran is a double-stranded siRNA formulated as a lipid nanoparticle for targeted delivery to hepatocytes. In the Phase III clinical trial Apollo, IV infusions with patisiran significantly changed the primary and secondary outcomes compared with placebo 11 and in the open-label extension 12 . A new formulation, revusiran, was designed to allow subcutaneous administration using a GAlNAC-conjugate nanovector instead of lipid nanoparticles 13 .…”