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EMA’s human medicines committee (CHMP) has recommended not renewing the conditional marketing authorisation for Translarna (ataluren), a medicine for treating patients with Duchenne muscular dystrophy. Translarna is used in patients whose disease is caused by a type of genetic defect called a ‘nonsense mutation’ in the dystrophin gene and who are able to walk.

The CHMP issued an initial negative opinion on the renewal of the marketing authorisation for Translarna in September 2023, which was confirmed in January 2024 following a re-examination requested by the company marketing the medicine. Both rounds of assessment concluded that the effectiveness of Translarna had not been confirmed following a re-evaluation of the medicine’s benefits and risks.

In May 2024, the European Commission asked the CHMP to further consider whether the data available on Translarna were sufficiently comprehensive to conclude on the medicine’s benefit-risk balance, and whether additional real-world data brought to the attention of the Commission during its decision-making process (including three recent publications) may impact the CHMP’s conclusion. In addition, following the appellate judgment of the Court of Justice of the European Union (EU) of 14 March 2024 in Case C-291/22 P, EMA decided to convene a new scientific advisory group on neurology (SAG) for Translarna. The assessment was therefore reset to this stage of the initial renewal procedure.

In relation to the request from the European Commission, the CHMP reviewed the recent publications, one of which analysed the combined data of three clinical studies with Translarna already assessed by the CHMP (meta-analysis);[1] a second evaluated the level of agreement amongst 12 clinicians on the use of Translarna;[2] and a third described an initiative to compile data on rare neuromuscular disorders.[3] The Committee also considered additional information received from parents or caregivers of boys affected by Duchenne muscular dystrophy, patient organisations, healthcare professional organisations, and treating doctors, as well as reports on individual patients treated with Translarna.

The CHMP carefully reviewed this information and concluded that it did not bring sufficient evidence to confirm the effectiveness of the medicine. In particular, the Committee noted that the methods used to carry out the meta-analysis had several shortcomings and its results could not overrule the negative findings of the individual studies included in the meta-analysis. The other two publications did not provide new data on the medicine’s effectiveness. The Committee therefore concluded that these additional data do not impact its previous conclusion on the benefit-risk balance of Translarna.

For the present opinion, the CHMP also considered the advice from the new scientific advisory group on neurology. This groups comprised experts, including neurologists and people with lived experience of Duchenne muscular dystrophy, who provided their views on specific questions posed by the CHMP. During the assessment, people with lived experience of Duchenne muscular dystrophy also presented their views to the CHMP during its plenary meetings.

In reaching its opinion, the CHMP took all the above information into account as well as the evidence accumulated on the medicine since its marketing authorisation in 2014. This evidence includes data from the main study that supported the authorisation and from two post-authorisation studies that were requested by the CHMP to confirm the medicine’s effectiveness.

The two post-authorisation studies failed to confirm the benefits of the medicine, including in patients with a progressive decline in their ability to walk who were expected to be more sensitive to treatment with Translarna. The CHMP also reviewed data from a study comparing two patient registries. However, due to differences between the two registries and uncertainty linked to the indirect comparison, no firm conclusion on the effectiveness of the medicine could be drawn from these real-world data and the Committee considered that this study cannot counterbalance the findings from the failed post-authorisation studies. After a thorough assessment of the totality of the data, the Committee concluded that the effectiveness of Translarna has not been confirmed in patients with nonsense mutation Duchenne muscular dystrophy.

The Committee acknowledged the high unmet medical need for an effective treatment for patients with this rare disease. However, it considered that the data available on Translarna, as described above, are comprehensive and concluded that the benefit-risk balance for this medicine is negative. It therefore recommended not renewing the marketing authorisation in the EU.

EMA will now send the CHMP opinion to the European Commission, which will issue a final legally binding decision applicable in all EU Member States.

Information for patients and carers

• Following a request from the European Commission, EMA’s CHMP has reviewed additional data in relation to the renewal of the marketing authorisation for Translarna, alongside all the available evidence on the medicine.
• These additional data included the results from three (3) recent publications, information received from parents or caregivers, patient organisations, healthcare professionals organisations and treating doctors, as well as reports on individual patients treated with Translarna.^1,2,3
• In addition, the CHMP considered the views from a scientific advisory group on neurology, which comprised experts, including neurologists and people with lived experience of Duchenne muscular dystrophy. This group provided responses to specific questions posed by the CHMP.
• The CHMP carefully reviewed all this information as well as the evidence accumulated on Translarna since its marketing authorisation in 2014. The Committee acknowledged the high unmet medical need for an effective treatment for patients with this rare disease; however, considering all the available evidence, it concluded that the effectiveness of Translarna has not been confirmed in patients with nonsense mutation Duchenne muscular dystrophy.
• Therefore, the Committee recommended not renewing Translarna’s marketing authorisation in the EU.
• This means that if this recommendation is confirmed by the European Commission, the medicine will no longer be authorised in the EU.
• Until then, the marketing authorisation for Translarna remains valid. If you have any questions, please speak with your doctor or contact your national competent authority.

Information for healthcare professionals

• Following a request from the European Commission, EMA’s CHMP has reviewed additional data in relation to the renewal of the marketing authorisation for Translarna, alongside all the available evidence on the medicine.
• These additional data included:

- three recent publications: a meta-analysis of three (3) clinical trials with Translarna (study 007, study 020 and study 041); an article on a newly-established registry bringing together data on rare neuromuscular disorders; and a study on the level of consensus amongst 12 clinicians on the use of Translarna;^1,2,3

- additional information received from parents or caregivers, patient organisations, healthcare professionals organisations, and treating doctors;

- reports with subject-level data related to boys treated with Translarna.

• The CHMP carefully reviewed all this information and concluded that it did not bring sufficient evidence to confirm the effectiveness of the medicine.
• The Committee noted in particular that the meta-analysis, which was already reviewed and discussed by the CHMP, has several methodological shortcomings, so its results cannot overrule the negative findings of the individual studies. The publication concerning rare neuromuscular disorders did not discuss the effectiveness of Translarna, while the publication regarding the level of agreement amongst neurologists did not provide new data on the medicine’s effectiveness.
• In addition, the CHMP took into account the views from a scientific advisory group on neurology, which comprised experts, including neurologists and people with lived experience of Duchenne muscular dystrophy. The group provided responses to specific questions posed by the CHMP.
• In reaching its opinion, the CHMP took all this information and the evidence accumulated on Translarna since its marketing authorisation into consideration.
• The Committee acknowledged the high unmet medical need for an effective treatment for patients with this rare disease; however, considering all the available evidence, it concluded that the effectiveness of Translarna has not been confirmed in patients with nonsense mutation Duchenne muscular dystrophy.
• Therefore, the Committee recommended not renewing Translarna’s marketing authorisation in the EU.
• This means that if this recommendation is confirmed by the European Commission, the medicine will no longer be authorised in the EU.
• Until then, the marketing authorisation for Translarna remains valid in the EU. If you have any questions, you may contact your national competent authority.

More about the medicine

Translarna received a conditional marketing authorisation in the EU on 31 July 2014 for the treatment of patients with Duchenne muscular dystrophy whose disease is caused by a ‘nonsense mutation’ in the dystrophin gene.

Duchenne muscular dystrophy is a serious and rare condition with no authorised treatment, apart from Translarna. It is a genetic disease that causes a gradually increasing weakness and loss of muscle function, leading to death due to respiratory muscle weakness or cardiomyopathy. Patients with this disease lack normal dystrophin, a protein found in muscles that helps protect muscles from injury as they contract and relax.

In patients with Duchenne muscular dystrophy caused by a nonsense mutation, production of a normal dystrophin protein is stopped prematurely, leading to a shortened dystrophin protein that does not function properly. The active substance in Translarna, ataluren, is expected to work by enabling the protein-making apparatus in cells to move past the genetic mutation, allowing the cells to produce a functional dystrophin protein. More information on Translarna is available on the medicine’s page on the EMA website.

More about the procedure

The renewal of the marketing authorisation application for Translarna was assessed by EMA’s Committee for Medicinal Products for Human Use (CHMP), responsible for questions concerning medicines for human use, which adopted EMA’s initial opinion on 14 September 2023.

The company that markets Translarna asked for re-examination of the CHMP’s opinion on the renewal application on 4 October 2023. After conducting the re-examination, the CHMP issued its final opinion on 25 January 2024 which was forwarded to the European Commission for a final legally binding decision.

On 24 May 2024, the European Commission asked the Committee to further consider whether the data available on Translarna were sufficiently comprehensive to conclude on the medicine’s benefit-risk balance, and whether additional real-world data brought to the attention of the Commission during its decision-making process might have impacted the CHMP conclusion on the benefit/risk profile of Translarna.

In addition, following the appellate judgment of the Court of Justice of the European Union of 14 March 2024 in Case C-291/22 P, EMA decided to convene a new scientific advisory group on neurology (SAG-N) for Translarna. The assessment was therefore reset to this stage of the initial renewal procedure.

EMA will now send the CHMP opinion on the renewal application to the European Commission for a final legally binding decision applicable in all EU Member States.

The company that markets Translarna may ask for re-examination within 15 days of receiving the opinion.

(DC/GS)