Five-Year Results With Patisiran for Hereditary Transthyretin Amyloidosis With Polyneuropathy
DOI:
10.1001/jamaneurol.2024.4631
Publication Date:
2025-01-13T16:01:27Z
AUTHORS (307)
ABSTRACT
Importance There is a lack of long-term efficacy and safety data on hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN) RNA interference (RNAi) therapeutics in general. This study presents the longest-term to date patisiran for hATTR-PN. Objective To present adults Design, Setting, Participants global open-label extension (OLE) APOLLO randomized clinical trial phase 2 OLE enrolled patients from 43 hospitals or centers across 19 countries between July 2015 August 2017, follow-up until November 2022. Of 212 eligible hATTR who completed 3 parent studies, 211 138 OLE. Intervention Patisiran, 0.3 mg/kg, intravenously once every weeks up 5 years. Main Outcomes Measures evaluated at year included disability (polyneuropathy [PND] score); severity (Neuropathy Impairment Score [NIS]), nutritional status (modified body mass index [mBMI]), quality life (Norfolk Quality Life–Diabetic Neuropathy [Norfolk QOL-DN]), Rasch-Built Overall Disability Scale (R-ODS), no statistical hierarchy. Safety, survival probability, mortality were also assessed. Results At baseline, mean (SD) age was 61.3 (12.3) years, 156 (73.9%) male. In completing study, PND scores remained stable improved 89 (65.0%), NISs showed change 10.9 (14.7), mBMI (calculated as weight kilograms divided by height meters squared times serum albumin grams per liter) increased 46.4 (120.7) over years baseline. Norfolk QOL-DN R-ODS changes 4.1 (16.7) –3.7 (6.2), respectively. Adverse events (AEs) leading withdrawal occurred 47 (22.3%). Infusion-related reactions most common treatment-related AE (n = 34 [16.1%]). Overall, 41 (19.4%) died during study. Patisiran treatment low familial amyloid score baseline associated significantly survival. Conclusions Relevance longest an RNAi therapeutic any disease, resulted modest hATTR-PN acceptable profile. These results highlight importance initiating early potential medicine. Trial Registration ClinicalTrials.gov Identifier: NCT02510261
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