The European Medicines Agency (EMA) has confirmed its earlier recommendation against renewing the conditional marketing authorization for Translarna (ataluren), a drug used to treat Duchenne muscular dystrophy (DMD) in patients with a specific genetic defect known as a 'nonsense mutation' in the dystrophin gene who are still able to walk. This decision follows a comprehensive re-evaluation of Translarna's benefits and risks. The EMA's Committee for Medicinal Products for Human Use (CHMP) concluded that the drug's effectiveness had not been sufficiently demonstrated.
Lack of Confirmed Efficacy
The re-examination, prompted by a request from the company marketing Translarna, included a reassessment of data from study 041, a post-authorization study, and a comparison of two patient registries. Study 041, a Phase 3, randomized, double-blind, placebo-controlled trial, did not show a statistically significant benefit for Translarna in patients with a progressive decline in their ability to walk. In this subgroup, the distance walked in six minutes after 18 months decreased by approximately 82 meters in the Translarna group versus 90 meters in the placebo group (p=0.36). The CHMP also noted that additional studies did not confirm Translarna's mechanism of action, showing only a minimal effect on dystrophin protein production.
Patient Registry Data Uncertainties
The assessment of data from a study comparing the health outcomes of patients from the STRIDE registry (Translarna-treated) and the CINRG DNHS registry (untreated) was a crucial part of the re-examination. While results suggested that patients in the STRIDE registry lost their ability to walk approximately 3.5 years later than those in the CINRG DNHS registry, the CHMP identified several issues and uncertainties that prevented them from attributing this difference to Translarna's effect. These uncertainties included differences in the timing of the registries, potentially allowing STRIDE patients to benefit from more recent advances in non-pharmacological treatments like physiotherapy. There were also concerns about how differences in steroid use, the standard of care for DMD, were accounted for in the analysis, as well as differences in the genetic mutations causing DMD between the two registry populations.
CHMP's Final Decision
Despite acknowledging the high unmet medical need for effective DMD treatments and considering input from neurology experts, patient representatives, families, physicians, and healthcare organizations, the CHMP concluded that the totality of evidence accumulated since Translarna's authorization did not confirm its effectiveness in DMD patients with nonsense mutations. The committee determined that Translarna's benefit-risk balance is negative and recommended against renewing its marketing authorization in the EU. The EMA has forwarded the CHMP's opinion to the European Commission, which will issue a final, legally binding decision applicable in all EU Member States. Healthcare professionals are advised not to initiate Translarna treatment in new patients and to discuss ongoing care with patients currently receiving the drug.
