Five-Year Results With Patisiran for Hereditary Transthyretin Amyloidosis With Polyneuropathy: A Randomized Clinical Trial With Open-Label Extension
Journal
JAMA Neurology
Journal Volume
82
Journal Issue
3
Start Page
228
End Page
236
ISSN
2168-6149
Date Issued
2025-03-10
Author(s)
David Adams
Jonas Wixner
Michael Polydefkis
John L. Berk
Isabel M. Conceição
Angela Dispenzieri
Amanda Peltier
Mitsuharu Ueda
Shaun Bender
Kelley Capocelli
Patrick Y. Jay
Elena Yureneva
Laura Obici
Giuseppe Vita
Vincenzo Rizzo
Massimo Russo
Anna Mazzeo
Luca Gentile
John L Berk
Janice Wiesman
Michelle Kaku
Vincent Lau
Douglas DeLong
James Dalton
John May
Shahram Attarian
Emilien Delmont
Jean Pouget
Annie Verschueren
Aude-Marie Grapperon
Emmanuelle Campana-Salort
Isabel M Conceição
Carlos Neves
Miguel O Santos
Conceição de Azevedo Coutinho
Catarina Falcao de Campos
Teresa Coelho
Antonio H Reis
Nuno Correia
Javier M Perez
Ana Martins da Silva
Cristina Alves
Marcio Cardoso
Katia Valdrez
Julia R Monte
Marta Novais
Nadia Guimaraes
Ines Cardoso
Monica Freitas
Joana Ramalho
Natalia Ferreira
Daisuke Kuzume
Masahiro Yamasaki
Yuko Morimoto
Celine Tard
Eric Hachulla
Clement Gauvain
Maria-Claire Migaud-Chervy
Dominique Deplanque
Elsa Jozefowicz
Loic Lebellec
David Adams
Marie Théaudin-Saliou
Cécile Cauquil-Michon
Celine Labeyrie
Adeline Not
Abdallah Al-Salameh
Anne-Lise Lecoq
Maeva Stephant
Andoni Echaniz-Laguna
Laurent Becquemont
Guillemette Beaudonnet
Vincent Algalarrondo
Ludivine Eliahou
Michel S Slama
Antoine Rousseau
Aissatou Signate
Paola Darche
Jerome Grimaud
Emeline Berthelot
Jocelyn Inamo
Violaine Planté-Bordeneuve
Thierry Gendre
Raphaele Arrouasse
Samar S Ayache
Laura Ernande
Philippe Le Corvoisier
Hayet Salhi
Ariane Choumert
Cyril Charlin
Thomas Megelin
Thomas H Brannagan III
Steven Tsang
Fernanda Wajnsztajn
Jeffrey Shije
Christina Ulane
Inna Kleyman
Louis Weimer
Comana Cioroiu
Kleopas Kleopa
Eleni Zamba-Papanicolaou
Satoshi Tada
Masahiro Nagai
Rina Ando
Yuki Yamanishi
J Scott Overcash
Sinikka Green
Michael Waters
Derya J Coskun
Paul Manos
Karla A Zepeda
William O’Riordan
Laura Obici
Andrea Cortese
Alessandro Lozza
Giampaolo Merlini
Vittorio Rosti
Mario Sabatelli
Giulia Bisogni
Daniela Bernardo
Marco Luigetti
Andrea Di Paolantonio
Valeria Guglielmino
Angela Romano
Hans Nienhuis
Arnt V Kristen
Christian Nagel
Fabian aus dem Siepen
Selina Hein
Shuichiro Neshige
Josep M Campistol
Lida Maria Rodas Marin
Josep Miquel Blasco Pelicano
Lucía Galán Dávila
Vanesa Pytel Cordoba
Antonio Guerrero Sola
Alejandro Horga
Julián García Feijoo
Leopoldo Perez de Isla
Wilson Marques Júnior
Carolina Lavigne Moreira
Vanessa Daccach Marques
Francisco Munoz Beamud
Cristina Borrachero
Inés AL López
Monica Sanz
Elena Rigo Oliver
Juan González Moreno
Jose M Gamez Martinez
Cristina Descals
Mercedes Uson
Francisco Jose Vega
Antoni Figuerola
Carles Montala
Márcia Waddington-Cruz
Aline Souza de Abreu
Moises Dias da Silva
Renata Gervais de Santa Rosa
Marcus Vinicius Pinto
Amanda Cardoso Berensztejn
Luiz Felipe Pinto
Mariana de Andrade Guedes
Fabio Barroso
Andrea Lautre
Lucas G Orellana
Maria Alejandra González-Duarte Briseño
Karla Cárdenas-Soto
Carlos Gerardo Cantú Brito
David Rivera de la Parra
Jose Pablo Hernandez Reyes
Maria del Mar Saniger Alba
Yesim Parman
Erdi Sahin
Nail G Serbest
Hacer Durmus
Arman Cakar
Sacit Karamursel
Ali Elitok
Nermin G Sirin Inan
Emre Altinkurt
Michael Polydefkis
Adriane C Allen
Vinay Chaudhry
Raquel Jarrett
Neil Bressler
Mandeep Singh
Mohammad Khoshnoodi
Daniel P Judge
Alvin T Lui
Tae Hwan Chung
Geno Vista
Syed Mahmood Shah
Hirotoshi Hamaguchi
Tetsuya Oda
Masahiro Shimomura
Christof Scheid
Udo Holtick
Jeeyoung Oh
Hee Jin Kim
Hyun Jin Shin
Kyomin Choi
Mitsuharu Ueda
Yohei Misumi
Toshiya Nomura
Takahisa Tateishi
Elizabeth A Mauricio
Elliot Dimberg
Leslie T Cooper
Angela Dispenzieri
Amie Fonder
Miriam Hobbs
Peter Dyck
Wilson Gonsalves
Nelson Leung
Thomas E Witzig
Lisa Hwa
Prashant Kapoor
Shaji K Kumar
Yi Lin
Vincent S Rajkumar
David Dingli
Morie A Gertz
Peter J Dyck
Linde Gove
Samir Dalia
David Croy
Tim Holding
Peter Gorevic
Senda Ajroud-Driss
Robert Sufit
John-Michael Li
Miriam Freimer
Samantha LoRusso
Yasuhiro Aso
Byoung-Joon Kim
JuHyeon Kim
Ga Yeon Lee
Eun Bin Cho
Eun-Seok Jeon
Ju-Hong Min
Jin Myoung Seok
Hye Lim Lee
Jae Hong Park
Yoshiki Sekijima
Nagaaki Kato
Dai Kishida
Akiyo Hineno
Minori Kodaira
Tsuneaki Yoshinaga
Ken Takasone
Teruyoshi Miyahara
Yusuke Takahashi
Akira Imai
Kazuhiko Matsumoto
Kon-Ping Lin
Yi-Chung Lee
Jonas Wixner
Bjorn Pilebro
Ole Suhr
Intissar Anan
Erik Nordh
Fatima Pedrosa-Domellöf
Maria Chermenina
Anneli Nygren
Ivaylo Tournev
Sashka Zhelyazkova-Glaveeva
Zheyna Cherneva
Staiko Sarafov
Teodora Chamova
Sylvia Cherninkova-Gopina
Hartmut H Schmidt
Elena Vorona
Anna Huesing-Kabar
Matthias Schilling
Iyad Kabar
Phil-Robin Tepasse
Julian D Gillmore
Ana Martinez-Naharro
Liza Chacko
Oliver Cohen
Steven Law
Tamer Rezk
Helen J Lachmann
Dianna Quan
Stacy Dixon
Vera Fridman
Soon Chai Low
Khean Jin Goh
Michelle M Mezei
Kristin Jack
N. Kevin Wade
Glenn Lopate
Stephanie Geisler
R. Brian Sommerville
Julaine Florence
Graeme Stewart
Mark Taylor
Daniel Suan
Abstract
Importance
There is a lack of long-term efficacy and safety data on hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN) and on RNA interference (RNAi) therapeutics in general. This study presents the longest-term data to date on patisiran for hATTR-PN.
Objective
To present the long-term efficacy and safety of patisiran in adults with hATTR-PN.
Design, Setting, and Participants
This global open-label extension (OLE) of the APOLLO randomized clinical trial and phase 2 OLE study enrolled patients from 43 hospitals or clinical centers across 19 countries between July 2015 and August 2017, with follow-up until November 2022. Of 212 eligible patients with hATTR who completed the phase 3 APOLLO or phase 2 OLE parent studies, 211 enrolled in and 138 completed the global OLE.
Intervention
Patisiran, 0.3 mg/kg, intravenously once every 3 weeks for up to 5 years.
Main Outcomes and Measures
Outcomes evaluated at year 5 of the global OLE included disability (polyneuropathy disability [PND] score); polyneuropathy severity (Neuropathy Impairment Score [NIS]), nutritional status (modified body mass index [mBMI]), quality of life (Norfolk Quality of Life–Diabetic Neuropathy [Norfolk QOL-DN]), and Rasch-Built Overall Disability Scale (R-ODS), with no statistical hierarchy. Safety, survival probability, and mortality were also assessed.
Results
At the global OLE baseline, the mean (SD) age was 61.3 (12.3) years, and 156 patients (73.9%) were male. In 138 patients completing the study, PND scores remained stable or improved in 89 patients (65.0%), NISs showed a mean (SD) change of 10.9 (14.7), and mean (SD) mBMI (calculated as weight in kilograms divided by height in meters squared times serum albumin in grams per liter) increased by 46.4 (120.7) over 5 years from baseline. Norfolk QOL-DN and R-ODS scores showed mean (SD) changes of 4.1 (16.7) and –3.7 (6.2), respectively. Adverse events (AEs) leading to study withdrawal occurred in 47 patients (22.3%). Infusion-related reactions were the most common treatment-related AE (n = 34 [16.1%]). Overall, 41 patients (19.4%) died during the study. Patisiran treatment in the parent study and low familial amyloid polyneuropathy score at parent study baseline were associated with significantly improved survival.
Conclusions and Relevance
In the longest study of an RNAi therapeutic for any disease, patisiran treatment resulted in modest changes for patients with hATTR-PN with an acceptable safety profile. These results highlight the importance of initiating early treatment for hATTR and the potential of RNAi therapeutics in medicine.
Trial Registration
ClinicalTrials.gov Identifier: NCT02510261
SDGs
Publisher
American Medical Association (AMA)
Type
journal article