After re-examining available data, the European Medicine Agency’s human medicines committee (CHMP) has confirmed its previous recommendation to not renew the conditional marketing authorisation for the medication Translarna (ataluren).
This last round of assessment concluded that the effectiveness of Translarna has not been confirmed.
Translarna is used for treating patients with Duchenne muscular dystrophy aged two years and older who are able to walk and whose disease is caused by a type of genetic defect called a “nonsense mutation” in the dystrophin gene.
The CHMP issued an initial negative opinion on Translarna in September 2023, which was confirmed in January 2024 after a first re-examination requested by the company marketing the medicine.
In June this year, the Committee revisited its opinion at the request of the European Commission to take into account additional real-world data brought to the attention of the Commission during the decision-making process and consider whether the available data are comprehensive.
The views of a new scientific advisory group were also considered. However, after this assessment the CHMP recommendation remained negative.
The company then requested another re-examination, and the CHMP re-assessed the results from a study carried out after authorisation as a specific obligation (study 041) as well as patient registries data, taking into account new analyses provided by the company.
Results from study
Study 041 was the second study carried out after authorisation that aimed to confirm the benefits of Translarna. The first post-authorisation study (study 020), carried out earlier, had failed to confirm the effectiveness of Translarna but suggested that a subgroup of patients, those with a progressive decline in their ability to walk, might be more sensitive to the treatment.
The main objective of study 041 was therefore to look at the effect of Translarna in this subgroup of patients.
The results showed that the distance patients could walk in six minutes after 18 months of treatment decreased by about 82m in the Translarna group compared with 90m in the placebo group, however, this difference was not statistically significant, meaning that it may be due to chance.
Similarly, when looking at the decline in motor functions after about 18 months as measured using a standard scale called North Star Ambulatory Assessment (NSAA), the difference between patients treated with Translarna and those who received placebo was also not statistically significant.
The CHMP therefore concluded that study 041 had failed to confirm the effectiveness of the medicine.
Patient registries data
As part of this latest re-examination, the CHMP also reassessed data from a study comparing the health outcomes of patients from two registries. In the study, patients from the STRIDE registry were treated with Translarna for an average of 5.5 years between 2015 and 2022, while patients from the CINRG DNHS registry were not treated with Translarna and were followed up between 2006 and 2016.
The CHMP considered new analyses and data from the literature provided by the company.
Although the results suggested a delay in the loss of ability to walk in some patients treated with Translarna compared with those in the CINRG DNHS registry, the Committee could not draw conclusions on the benefits of Translarna from these data because of several differences between the registries and biases making the comparison inconclusive.
Furthermore, the Committee considered that these data do not outweigh the negative results of the two post-authorisation studies (study 041 and study 020).
In addition to these conclusions, the CHMP also noted that the mechanism of action of Translarna was not confirmed in additional studies, which showed only a very small effect of Translarna on the production of the dystrophin protein.
Throughout its review of Translarna, the CHMP consulted parents of boys and men with Duchenne muscular dystrophy of different ages. They were invited to meetings as patient experts along with other experts, including neurologists, to describe what it is like to live with this disease, and they spoke directly to the CHMP on several occasions.
The patients’ and parents’ perspectives have been sought and captured at every stage of the evaluation of this medicine. The Committee also considered all third-party information received from parents and caregivers of boys affected by Duchenne muscular dystrophy, patient organisations, healthcare professional organisations and treating doctors.
The CHMP acknowledges the high unmet medical need for an effective treatment for patients with Duchenne muscular dystrophy.
However, based on all the evidence accumulated, it concluded that the effectiveness of Translarna has not been confirmed in patients with Duchenne muscular dystrophy caused by a nonsense mutation, including those who were expected to have a better response to treatment.
The CHMP considered that the data now available are comprehensive and recommended not renewing the medicine’s marketing authorisation in the EU.
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.
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