The European Medicines Agency (EMA) has re-confirmed its decision not to renew the conditional marketing authorization for Translarna (ataluren), a drug used to treat Duchenne muscular dystrophy (DMD) caused by nonsense mutations. This decision follows a series of re-examinations by the EMA's Committee for Medicinal Products for Human Use (CHMP), which concluded that the effectiveness of Translarna has not been sufficiently demonstrated.
Lack of Confirmed Efficacy
The CHMP's decision was based on a reassessment of data from multiple sources, including post-authorization studies and patient registries. Key among these was Study 041, a Phase 3 clinical trial designed to confirm Translarna's benefits. The results of Study 041 indicated that, after 18 months of treatment, the difference in the distance patients could walk in six minutes between the Translarna group and the placebo group was not statistically significant (p=0.36). Similarly, there was no statistically significant difference in the decline of motor functions as measured by the North Star Ambulatory Assessment (NSAA).
Patient registry data from the STRIDE registry (Translarna-treated) and the CINRG DNHS registry (untreated) were also analyzed. While some results suggested a delay in the loss of walking ability in Translarna-treated patients, the CHMP found the comparison inconclusive due to differences between the registries and potential biases. The CHMP concluded that these registry data did not outweigh the negative results from the post-authorization studies.
Mechanism of Action Doubts
In addition to the clinical trial data, the CHMP noted that additional studies had not confirmed Translarna's mechanism of action, with only a very small effect observed on the production of the dystrophin protein. Dystrophin is critical for muscle function, and DMD is caused by mutations in the dystrophin gene.
Patient and Expert Input
Throughout the review process, the CHMP consulted with parents of boys and men with DMD, neurologists, and other healthcare professionals. Patient and parent perspectives were sought at every stage, and the committee considered all third-party information received from patient organizations and treating doctors. The CHMP acknowledged the high unmet medical need for effective DMD treatments but maintained that the available evidence did not confirm Translarna's effectiveness.
Implications and Next Steps
The EMA will now send the CHMP’s opinion to the European Commission, which will issue a final legally binding decision applicable in all EU Member States. In the meantime, PTC Therapeutics, the company marketing Translarna, has stated its commitment to ensuring the drug remains available to patients pending the European Commission's review.
Matthew B. Klein, MD, CEO of PTC, expressed disappointment with the CHMP's decision, stating that the committee based its decision on a subset of data from Study 041 rather than the totality of evidence, which includes data from three placebo-controlled trials and the STRIDE registry. He also noted that the decision goes against the wishes of physicians, patients, and families throughout Europe.
