Bello Luca, Riguzzi Pietro, Albamonte Emilio, Astrea Guja, Battini Roberta, Barp Andrea, Berardinelli Angela L, Bertini Enrico S, Brolatti Noemi, Bruno Claudio, Corti Stefania, D'Amico Adele, D'Angelo Maria Grazia, Dallavalle Gianfranco, Liguori Rocco, Maggi Lorenzo, Magri Francesca, Mancuso Michelangelo, Masson Riccardo, Mercuri Eugenio, Minetti Carlo, Messina Sonia, Mongini Tiziana, Musumeci Olimpia, Nigro Vincenzo, Pane Marika, Panicucci Chiara, Pedemonte Marina, Pini Antonella, Politano Luisa, Previtali Stefano, Ricci Federica, Ricci Giulia, Ruggiero Lucia, Sansone Valeria, Siciliano Gabriele, Trabacca Antonio, Trucco Federica, Velardo Daniele, Pegoraro Elena, Comi Giacomo P
Department of Neurosciences, DNS Clinica Neurologica, Azienda Ospedale University of Padova, via Giustiniani, 5, 35121, Padua, Italy.
The NeMO Center in Milan, Neurorehabilitation Unit, ASST Niguarda Hospital, University of Milan, Milan, Italy.
Drugs R D. 2025 May 28. doi: 10.1007/s40268-025-00512-x.
The Italian Duchenne muscular dystrophy expert clinicians, gathered in the Italian Association of Myology (AIM), intend to express a position against the suspension of the Marketing Authorization of ataluren (Translarna) 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 The marketing authorization has been recently withdrawn by the European Commission following a recommendation from the Committee for Medicinal Products for Human Use of the European Medicines Agency.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 clinical trials are challenging because of the heterogenous complex slow-progressing nature of the disorders.
意大利杜氏肌营养不良症专家临床医生齐聚意大利肌病协会（AIM），打算就撤销阿他芦醇（Translarna）治疗无义突变型杜氏肌营养不良症的上市许可一事表明反对立场。欧洲委员会根据欧洲药品管理局人用药品委员会的建议，最近撤销了该上市许可。这一负面建议基于以下事实：阿他芦醇治疗无义突变型杜氏肌营养不良症的三项随机对照试验（007、020和041）在每项研究选定的主要结局（即6分钟步行距离）方面，均未在意向性治疗人群（007和020试验）以及041试验的一个亚组中显示出有利于该治疗的统计学显著差异。然而，观察到的差异始终有利于治疗，并且多项具有临床意义的次要结局在各项研究中均为阳性且具有统计学显著性。重要的是，规模最大且时间最长的III期研究（041）在更广泛的意向性治疗人群中显示出有利于阿他芦醇的统计学显著效果。此外，一项关于阿他芦醇“真实世界”治疗数据的长期登记研究（卓越登记与数据库战略目标，STRIDE）除了证实其安全性令人放心外，还表明患者的行走、上肢和呼吸功能得到了长期维持。我们认为，将阿他芦醇从欧洲市场撤出不仅会损害无义突变型杜氏肌营养不良症患者，还会损害整个神经肌肉领域，因为该领域的疾病具有异质性、复杂性且进展缓慢，使得临床试验颇具挑战性。
