The European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended against renewing the conditional approval of Translarna (ataluren) for treating Duchenne muscular dystrophy (DMD) in the European Union. This decision casts uncertainty on the future availability of the only approved therapy in the EU for DMD patients with nonsense mutations.
PTC Therapeutics, the developer of Translarna, expressed surprise and disappointment, emphasizing the drug's well-established safety and efficacy profile. Matthew B. Klein, MD, CEO of PTC, stated the decision is "most devastating for the hundreds of boys and young men in Europe with nonsense mutation DMD, for whom no other approved therapies are available."
Basis for the Negative Opinion
The CHMP's negative opinion stems largely from data from the Phase 3 Study 041 (NCT03179631), a requirement for Translarna's conditional approval. The trial involved 359 boys with nonsense mutation DMD who were ambulatory. While the overall patient group showed statistically significant improvements in walking distance compared to placebo, the primary analysis population—patients able to walk at least 300 meters and stand for five seconds at baseline—did not show a significant effect.
Additional analyses considered data from earlier trials and the STRIDE registry, which tracked 300 boys for over 5.5 years. STRIDE data suggested that Translarna-treated patients retained walking ability for approximately 3.5 years longer than untreated individuals. However, concerns were raised regarding the robustness of the STRIDE registry data.
Translarna's Mechanism and Regulatory History
DMD results from mutations in the dystrophin gene, with about 15% of cases involving nonsense mutations that prematurely halt protein production. Translarna is an oral therapy designed to allow cells to bypass these premature stop signals, enabling the production of functional dystrophin protein.
Translarna received conditional approval in the EU in 2014 for patients aged 2 years and older with nonsense mutation DMD who are able to walk. This approval was renewed in 2017. The current CHMP decision puts this authorization at risk.
Next Steps for PTC Therapeutics
PTC plans to request a re-examination of the CHMP's opinion, as they have done previously in Translarna's regulatory history in Europe. The company intends to focus on what it describes as "clear and consistent evidence of benefit" from data collected from approximately 700 DMD patients treated with Translarna in clinical trials. PTC will also address issues related to Study 041 and concerns about the STRIDE registry data.
According to EMA guidelines, a revised opinion following the re-examination is expected in January 2024. Translarna will remain available in the EU market while the review is underway. If the CHMP maintains its negative opinion after re-examination, it will take effect approximately two months after the final opinion is issued.
Global Regulatory Landscape
Translarna holds conditional approvals in other regions, including Brazil and Russia. However, an application for its approval in the United States was rejected in 2017 due to concerns about demonstrating the therapy's effectiveness.
