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

Background Hereditary transthyretin-mediated amyloidosis is a rare, inherited, progressive disease caused by mutations in the transthyretin (TTR) gene. We assessed safety and efficacy of long-term treatment with patisiran, an RNA interference therapeutic that inhibits TTR production, patients hereditary polyneuropathy. Methods This multicentre, open-label extension (OLE) trial enrolled at 43 hospitals or clinical centres 19 countries as Sept 24, 2018. Patients were eligible if they had completed phase 3 APOLLO 2 OLE parent studies tolerated study drug. Eligible from (patisiran placebo groups) group) this global received patisiran 0·3 mg/kg intravenous infusion every weeks plans to continue do so for up 5 years. Efficacy assessments included measures polyneuropathy (modified Neuropathy Impairment Score +7 [mNIS+7]), quality life, autonomic symptoms, nutritional status, disability, ambulation motor function, cardiac stress, analysis groups (APOLLO-placebo, APOLLO-patisiran, patisiran) based on allocation trial. The ongoing no new enrolment, current findings are interim who 12-month data cutoff. Safety analyses all one more dose registered ClinicalTrials.gov, NCT02510261. Findings Between July 13, 2015, Aug 21, 2017, 212 patients, 211 enrolled: 137 APOLLO-patisiran group, 49 APOLLO-placebo 25 group. At cutoff 2018, 126 (92%) 38 (78%) (100%) group assessments. 12 months, improvements mNIS+7 sustained baseline (APOLLO-patisiran mean change –4·0, 95 % CI –7·7 −0·3; –4·7, –11·9 2·4). Mean score improved enrolment (mean −1·4, 95% –6·2 3·5). Overall, 204 (97%) reported adverse events, 82 (39%) serious there 23 (11%) deaths. Serious events frequent (28 [57%] 49) than (48 [35%] 137) (six [24%] 25) groups. most common treatment-related event was mild moderate infusion-related reactions. frequency deaths higher (13 [27%] 49), burden (ten [7%] (0 Interpretation In study, appeared maintain acceptable profile Continued follow-up will be important overall assessment patisiran. Funding Alnylam Pharmaceuticals.