The European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended against renewing the conditional marketing authorization for Translarna (ataluren), a drug used to treat Duchenne muscular dystrophy (DMD) in patients with nonsense mutations in the dystrophin gene who are still able to walk. This decision follows a comprehensive re-evaluation of the drug's benefits and risks, initiated after an initial negative opinion in September 2023 and a subsequent re-examination in January 2024. The CHMP's assessment, reset after a European Court of Justice ruling, concludes that the effectiveness of Translarna has not been confirmed.
Comprehensive Review of Available Data
The CHMP's decision was informed by a thorough review of recent publications, including a meta-analysis of three clinical studies involving Translarna, an evaluation of clinician agreement on Translarna's use, and a description of a rare neuromuscular disorder data initiative. The committee also considered additional information from parents, caregivers, patient organizations, healthcare professionals, and individual patient reports. Despite these efforts, the CHMP found that the new data did not provide sufficient evidence to confirm the drug's effectiveness. The committee specifically noted methodological shortcomings in the meta-analysis, which prevented it from overriding the negative findings of individual studies.
Input from Scientific Advisory Group and Patient Perspectives
For this opinion, the CHMP also considered advice from a new Scientific Advisory Group on Neurology (SAG), comprising experts, including neurologists and individuals with lived experience of Duchenne muscular dystrophy. These experts provided their views on specific questions posed by the CHMP. Furthermore, individuals with lived experience of Duchenne muscular dystrophy presented their perspectives to the CHMP during plenary meetings, ensuring a comprehensive understanding of the patient experience.
Lack of Confirmed Efficacy
The CHMP's decision was based on a comprehensive assessment of data accumulated since Translarna's initial marketing authorization in 2014. This included data from the original study supporting the authorization and two post-authorization studies requested by the CHMP to confirm the drug's effectiveness. These post-authorization studies failed to confirm the benefits of Translarna, even in patients with a progressive decline in their ability to walk, who were expected to be more responsive to the treatment. A study comparing two patient registries also failed to provide conclusive evidence of the drug's effectiveness due to inherent differences between the registries and uncertainties related to the indirect comparison.
Implications for Patients and Healthcare Professionals
The CHMP acknowledged the significant unmet medical need for effective treatments for Duchenne muscular dystrophy, a rare genetic disease characterized by progressive muscle weakness and loss of function. However, the committee concluded that the available data on Translarna did not demonstrate a positive benefit-risk balance, leading to the recommendation against renewing its marketing authorization in the EU. The EMA will now forward the CHMP's opinion to the European Commission, which will issue a final, legally binding decision applicable in all EU Member States. Until then, Translarna's marketing authorization remains valid. Patients and healthcare professionals with questions are encouraged to consult their doctors or national competent authorities.
