Citations 1
Five-Year Results With Patisiran for Hereditary Transthyretin Amyloidosis With Polyneuropathy
Wixner, Jonas , Polydefkis, Michael , Ueda, Mitsuharu , Bender, Shaun, Jay, Patrick Y. , Yureneva, Elena, group, patisiran Global OLE study, Vita, Giuseppe, Rizzo, Vincenzo , Wiesman, Janice F. , Lau, Vincent , DeLong, Douglas, May, John J., Delmont, Émilien , Pouget, Jean, Grapperon, Aude‐Marie , Campana-Salort, Emmanuelle, Coutinho, Conceição de Azevedo, Campos, Catarina Falcão de , Coelho, Teresa , Reis, Antonio Hipólito, Pérez, Javier Martínez , Silva, Ana Martins da, Alves, Cristina , Cardoso, Márcio , Valdrez, Kátia, Monte, Julia R, Novais, Marta , Guimarães, Nádia, Cardoso, Inês , Freitas, Mónica, Ferreira, Natália , Kuzume, Daisuke , Morimoto, Yuko, Gauvain, Clément , Migaud-Chervy, Maria-Claire, Deplanque, Dominique , Jozefowicz, Elsa, Théaudin-Saliou, Marie, Cauquil-Michon, Cécile, Labeyrie, Céline , Not, Adeline , Lecoq, Anne-Lise , Stephant, Maeva, Echaniz‐Laguna, Andoni , Becquemont, Laurent , Beaudonnet, Guillemette , Eliahou, Ludivine , Slama, Michel , Signaté, Aïssatou , Darche, Paola, Grimaud, Jérôme, Berthelot, Emeline, Inamo, Jocelyn , Gendre, Thierry , Arrouasse, Raphaele , Ernande, Laura , Salhi, Hayet, Choumert, Ariane , Charlin, Cyril, Megelin, Thomas, Brannagan, Thomas H., Tsang, Steven, Wajnsztajn, Fernanda, Shije, Jeffrey, Ulane, Christina, Kleyman, Inna , Weimer, Louis H., Cioroiu, Comana , Kleopa, Kleopas A. , Zamba‐Papanicolaou, Eleni , Tada, Satoshi , Nagai, Masahiro , Ando, Rina, Yamanishi, Yuki , Overcash, J. Scott , Green, Sinikka, Coskun, Derya J, Manos, Paul S. , Zepeda, Karla A, O’Riordan, William, Cortese, Andrea , Bernardo, Daniela, Paolantonio, Andrea Di , Guglielmino, Valeria , Kristen, Arnt V. , Nagel, Christian , Siepen, Fabian aus dem , Hein, Selina , Campistol, Josep M. , Marín, Lida María Rodas, Pelicano, Josep Miquel Blasco, Dávila, Lucía Galán, Cordoba, Vanesa Pytel, Sola, A. Guerrero, Feijoo, Julián García, Isla, Leopoldo Pérez de , Moreira, Carolina Lavigne , Marques, Vanessa Daccach , Beamud, Francisco Muñoz, Borrachero, Cristina, Sanz, Mónica, Oliver, E, Moreno, Juan González, Martinez, J. Michael, Descals, Cristina, Usón, Mercedes, Vega, Francisco Jose, Figuerola, Antoni, Montalà, Carles, Abreu, Aline França de , Silva, Moises Dias da, Rosa, Renata Gervais de Santa, Berensztejn, Amanda Cardoso, Guedes, Mariana de Andrade, Lautre, Andrea, Orellana, Lucas, Briseño, Maria Alejandra González-Duarte, Parra, David Rivera de la, Reyes, Jose Pablo Hernandez, Alba, Maria del Mar Saniger, Parman, Yeşim , Serbest, Nail Güven , Durmuş, Hacer , Karamürsel, Saçit , Elitok, Ali, Inan, Nermin G Sirin, Altinkurt, Emre, Polydefkis, Michael, Allen, Adriane C, Chaudhry, Vinay , Jarrett, R. J., Bressler, Neil M. , Khoshnoodi, Mohammad , Lui, Alvin T, Chung, Tae , Vista, Geno, Shah, Syed Mahmood , Hamaguchi, Hirotoshi , Oda, Tetsuya , Shimomura, Masahiro, Kim, Hee Jin, Misumi, Yohei , Nomura, Toshiya , Tateishi, Takahisa , Mauricio, Elizabeth A. , Dimberg, Elliot L., Fonder, Amie , Hobbs, Miriam, Dyck, P. James B. , Leung, Nelson , Hwa, Yi L. , Kapoor, Prashant , Kumar, Shaji , Dingli, David , Gove, Linde E., Dalia, Samir , Croy, David, Holding, Tim, Gorevic, Peter D., Su, Jen-Jen , Lin, Chao-Wen, Ajroud‐Driss, Senda , Sufit, Robert , Li, John-Michael, Freimer, Miriam , LoRusso, Samantha, Aso, Yasuhiro , Kim, Byoung‐Joon , Kim, JuHyeon, Jeon, Eun‐Seok , Seok, Jin Myoung , Park, Jae Hong , Sekijima, Yoshiki , Kato, Naga-aki, Hineno, Akiyo , Kodaira, Minori , Yoshinaga, Tsuneaki , Takasone, Ken, Miyahara, Teruyoshi, Takahashi, Yusuke , Matsumoto, Kazuhiko , Lin, Kon-Ping, Lee, Yi‐Chung , Wixner, Jonas, Pilebro, Björn, Nordh, Erik, Chermenina, Maria, Nygren, Anneli, Tournev, Ivaylo, Zhelyazkova, Sashka , Cherneva, Zheyna , Sarafov, S., Cherninkova-Gopina, Sylvia, Vorona, Elena, Huesing-Kabar, Anna, Schilling, Matthias , Kabar, Iyad , Martinez–Naharro, Ana , Chacko, Liza , Cohen, Oliver , Law, Steven , Rezk, Tamer , Quan, Dianna , Dixon, Stacy, Fridman, Vera , Low, Soon-Chai , Mezei, Michelle M. , Jack, Kristin, Wade, N. Kevin, Lopate, Glenn, Geisler, Stephanie , Sommerville, R. Brian, Florence, Julaine, Stewart, Graeme J., Taylor, Mark , Suan, Daniel, Dingli, David , Gillmore, Julian D , Lee, Yi-Chung , Karamursel, Sacit , Adams, David , Berk, John L. , Conceição, Isabel , Dispenzieri, Angela , Peltier, Amanda , Bender, Shaun , Capocelli, Kelley, Obici, Laura , group, patisiran Global OLE study, Vita, Giuseppe, Russo, Massimo , Mazzeo, Anna Teresa , Gentile, Luca, Kaku, Michelle C. , Lau, Vincent, Dalton, James, May, John, Attarian, Shahram , Verschueren, Annie , Campana-Salort, Emmanuelle, Neves, Carlos, Santos, Miguel Oliveira , Coelho, Teresa, Correia, Nuno, Perez, Javier M, Silva, Ana Martins da, Ramalho, Joana, Yamasaki, Masahiro , Morimoto, Yuko, Tard, Céline , Hachulla, É. , Lebellec, Loïc , Théaudin, Marie , Al‐Salameh, Abdallah , Algalarrondo, Vincent , Rousseau, Antoine , Planté‐Bordeneuve, Violaine , Ayache, Samar S. , Corvoisier, Philippe Le , Waters, Michael, Manos, Paul, Lozza, Alessandro , Merlini, Giampaolo , Rosti, Vittorio , Sabatelli, Mario , Bisogni, Giulia , Luigetti, Marco , Romano, Ângela , Nienhuis, Hans L. A. , Neshige, Shuichiro , Horga, Alejandro , Feijoo, Julián García, Marques, Wilson , López, Inés AL, Sanz, Monica, Martinez, Jose M Gamez, Waddington‐Cruz, Márcia , Abreu, Aline Souza de, Silva, Moises Dias da, Pinto, Marcus Vinícius , Pinto, Luiz Felipe , Barroso, Fábio , Briseno, Maria Alejandra Gonzalez Duarte, Cárdenas‐Soto, Karla , Cantú-Brito, Carlos Gerardo , Şahin, Erdi , Çakar, Arman , İNAN, NERMİN GÖRKEM ŞİRİN, Polydefkis, Michael, Jarrett, Raquel, Singh, Mandeep , Judge, Daniel P. , Lui, Alvin T, Vista, Geno, Shimomura, Masahiro, Scheid, Christof , Holtick, Udo , Oh, Jeeyoung , Kim, Hee Jin, Shin, Hyun Jin , Choi, Kyomin , Mauricio, Elizabeth A. , Cooper, Leslie T. , Gonsalves, Wilson I. , Witzig, Thomas E. , Lin, Yi , Rajkumar, S. Vincent , Gertz, Morie A. , Chao, Chi‐Chao , Lee, Ming‐Jen , Hsieh, Sung‐Tsang , Tsai, Li‐Kai , Yeh, Shin‐Joe , Yang, Chih‐Chao , Lee, Ga-Yeon , Cho, Eun Bin , Min, Ju‐Hong , Lee, Hye Lim , Kishida, Dai , Imai, Akira, Lin, Kon‐Ping, Wixner, Jonas, Suhr, Ole B. , Anan, Intissar , Nordh, Erik, Domellöf, Fátima Pedrosa , Chamova, Teodora , Schmidt, Hartmut , Tepasse, Phil‐Robin , Gillmore, Julian D. , Lachmann, Helen J. , Goh, Khean Jin , Geisler, Stephanie, Taylor, Mark, Suan, Dan
JAMA Neurology | January 13, 2025 | Volume: 82 | Issue: 3 | Pages: 228
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