Opinion of the Italian Association of Myology on Ataluren for the Treatment of Nonsense Mutation Duchenne Muscular Dystrophy

作者：Luca Bello, Pietro Riguzzi, Emilio Albamonte, Guja Astrea, Roberta Battini, Andrea Barp, Angela Lucia Berardinelli, Enrico Bertini, Noemi Brolatti, Claudio Bruno, Stefania Paola Corti, Adele D’Amico, Maria Grazia D’Angelo, Gianfranco Dallavalle, Rocco Liguori, Lorenzo Maggi, Francesca Magri, Michelangelo Mancuso, Riccardo Masson, Eugenio Maria Mercuri, Carlo Minetti, Sonia Messina, Tiziana Mongini, Olimpia Musumeci, Vincenzo Nigro, Marika Pane, Chiara Panicucci, Marina Pedemonte, Antonella Pini, Luisa Politano, Stefano Carlo Previtali, Federica Ricci, Giulia Ricci, Lucia Ruggiero, Valeria Sansone, Gabriele Siciliano, Antonio Trabacca, Federica Trucco, Daniele Velardo, Elena Pegoraro, Giacomo P. Comi · 发表于：Drugs in R&D · 年份：2025 · DOI：10.1007/s40268-025-00512-x · 被引用次数：6 · 研究领域：Muscle Physiology and Disorders、Cardiomyopathy and Myosin Studies、Neurogenetic and Muscular Disorders Research

) for the treatment of nonsense mutation Duchenne muscular dystrophy. The marketing authorization has been recently withdrawn by the European Commission following a recommendation from the Committee for Medicinal Products for Human Use of the European Medicines Agency. This negative recommendation was based on the fact that three randomized controlled trials of ataluren in nonsense mutation Duchenne muscular dystrophy (007, 020, and 041) have failed to show statistically significant differencs in favor of the treatment in the selected primary outcomes for each individual study, i.e., 6-min walk distance, in the intent-to-treat population for 007 and 020 and in a subgroup for 041. However, observed differences always favored treatment, and several clinically meaningful secondary outcomes were positive and statistically significant across studies. Importantly, the largest and longest phase III study (041) showed a statistically significant effect in favor of ataluren in the wider intent-to-treat population. Furthermore, a long-term registry of "real-world" ataluren treatment data (Strategic Targeting of Registries and Database of Excellence, STRIDE), in addition to confirming a reassuring safety profile, suggested a prolonged maintenance of ambulatory, upper limb, and respiratory function. We deem that a withdrawal of ataluren from the European market would harm not only patients with nonsense mutation Duchenne muscular dystrophy, but the whole neuromuscular field, in which cli...