Title:
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Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis
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Author:
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Campistol Plana, Josep M.; González Duarte, Alejandra; Suhr, Ole B.; Goyal, Sunita; Gandhi, Pritesh J.; Polydefkis, Michael; Sekijima, Yoshiki; O'Riordan, William D.; Yang, Chih-Chao; Ueda, Mitsuharu; Kristen, Arnt V.; Coelho, Teresa; Berk, John L.; Lin, Kon Ping; Vita, Giuseppe; Attarian, Shahram; Planté Bordeneuve, Violaine; Mezei, Michelle M.; Buades, Juan; Brannagan, Thomas H.; Kim, Byoung J.; Oh, Jeeyoung; Parman, Yesim; Hawkins, Philip N.; Solomon, Scott D.; Dyck, Peter J.; Chen, Jihong; Strahs, Andrew L.; Nochur, Saraswathy V.; Sweetser, Marianne T.; Garg, Pushkal P.; Vaishnaw, Akshay K.; Gollob, Jared A.
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Other authors:
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Universitat de Barcelona |
Abstract:
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BACKGROUND Patisiran, an investigational RNA interference therapeutic agent, specifically inhibits hepatic synthesis of transthyretin. METHODS In this phase 3 trial, we randomly assigned patients with hereditary transthyretin amyloidosis with polyneuropathy, in a 2:1 ratio, to receive intravenous patisiran (0.3 mg per kilogram of body weight) or placebo once every 3 weeks. The primary end point was the change from baseline in the modified Neuropathy Impairment Score+7 (mNIS+7; range, 0 to 304, with higher scores indicating more impairment) at 18 months. Other assessments included the Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) questionnaire (range, −4 to 136, with higher scores indicating worse quality of life), 10-m walk test (with gait speed measured in meters per second), and modified body-mass index (modified BMI, defined as [weight in kilograms divided by square of height in meters]×albumin level in grams per liter; lower values indicated worse nutritional status). RESULTS A total of 225 patients underwent randomization (148 to the patisiran group and 77 to the placebo group). The mean (±SD) mNIS+7 at baseline was 80.9±41.5 in the patisiran group and 74.6±37.0 in the placebo group; the least-squares mean (±SE) change from baseline was −6.0±1.7 versus 28.0±2.6 (difference, −34.0 points; P<0.001) at 18 months. The mean (±SD) baseline Norfolk QOL-DN score was 59.6±28.2 in the patisiran group and 55.5±24.3 in the placebo group; the least-squares mean (±SE) change from baseline was −6.7±1.8 versus 14.4±2.7 (difference, −21.1 points; P<0.001) at 18 months. Patisiran also showed an effect on gait speed and modified BMI. At 18 months, the least-squares mean change from baseline in gait speed was 0.08±0.02 m per second with patisiran versus −0.24±0.04 m per second with placebo (difference, 0.31 m per second; P<0.001), and the least-squares mean change from baseline in the modified BMI was −3.7±9.6 versus −119.4±14.5 (difference, 115.7; P<0.001). Approximately 20% of the patients who received patisiran and 10% of those who received placebo had mild or moderate infusion-related reactions; the overall incidence and types of adverse events were similar in the two groups. CONCLUSIONS In this trial, patisiran improved multiple clinical manifestations of hereditary transthyretin amyloidosis. |
Subject(s):
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-Amiloïdosi -RNA -Assaigs clínics -Amyloidosis -RNA -Clinical trials |
Rights:
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(c) Massachusetts Medical Society, 2018
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Document type:
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Article Article - Published version |
Published by:
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Massachusetts Medical Society
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