Translarna approval for DMD in EU not recommended for renewal

Therapy developer PTC 'extremely disappointed,' to seek new review

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Multiple hands are seen giving a thumbs down sign against the backdrop of a red circle.

The conditional approval of Translarna (ataluren) in Europe as a treatment for Duchenne muscular dystrophy (DMD) — in place for nearly a decade — should now not be renewed, a committee of the European Medicines Agency (EMA) has recommended.

The EMA’s Committee for Medicinal Products for Human Use (CHMP) issued a negative opinion on a proposal that would convert Translarna’s conditional approval to a full approval. The negative opinion also applies to any renewal of the conditional approval.

Translarna, sold by PTC Therapeutics, has been conditionally authorized in the European Union since 2014 as a treatment for patients ages 2 and older who have DMD caused by a nonsense mutation and are able to walk. The conditional authorization had been renewed in 2017.

“We are surprised and extremely disappointed by the CHMP decision, given the well-established and favorable safety and efficacy profile of Translarna,” Matthew B. Klein, MD, CEO of PTC, said in a company press release.

PTC now is planning to submit a request for the CHMP to re-examine this opinion. In accordance with EMA guidelines, a revised opinion following the re-examination would be expected in January 2024.

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According to PTC, Translarna will remain available on the market in the EU while the company seeks a review of the committee’s opinion. If the CHMP’s opinion is still negative after the re-examination, it would go into effect about two months after the final opinion is issued.

“Of course, this 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,” Klein said, adding, “We will be submitting a request for re-examination to the CHMP to reverse this opinion, as we have done previously in the regulatory history of Translarna in Europe.”

The CHMP’s recommendations go to the EMA, which then sends its opinions to the European Commission, the EU’s regulatory body. The final decision issued by the European Commission will be legally binding for all EU member states.

This 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.


DMD is caused by mutations in the gene that provides instructions for making the protein dystrophin. About 15% of patients carry nonsense mutations, which cause an abnormal signal, basically a full stop, in the middle of the gene, sort of like putting a period in the middle of a sentence.

This early stop signal prevents production of a full-length dystrophin protein. Translarna, a daily oral therapy, is designed to make cells ignore the early stop signal to allow the production of functional dystrophin protein.

The CHMP’s negative opinion was based in large part on data from a Phase 3 trial called Study 041 (NCT03179631), which was conducted by PTC as a requirement of Translarna’s conditional approval in Europe. The study tested Translarna against a placebo in 359 boys with nonsense mutation DMD who were able to walk.

The trial’s main goal was to assess the effect of treatment on the distance that patients could walk in six minutes — a common measure of walking ability. Specifically, the study hoped to demonstrate an improvement in a subset of patients, called the primary analysis population, who were able to walk at least 300 meters (nearly 1,000 feet) and stay in a standing position for more than five seconds at the start of the trial.

The results showed that, in the overall group of patients, there were statistically significant improvements in walking distance for patients given Translarna versus a placebo. However, the study failed to show a significant effect in the primary analysis population.

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The new decision by the CHMP included analyses of data from earlier trials of Translarna, as well as findings from a real-world registry called STRIDE. That registry involved 300 boys with more than 5.5 years of treatment.

The researchers noted that, in STRIDE, patients who received Translarna retained the ability to walk for about 3.5 years longer than individuals not given the therapy.

In its call for a re-examination, PTC said it plans to focus on “the clear and consistent evidence of benefit” of Translarna based on data from the roughly 700 DMD boys who have been given the treatment in clinical trials.

The company also will address issues related to Study 041 and concerns raised about the robustness of data from the STRIDE registry.

Translarna also is conditionally approved in countries such as Brazil and Russia. However, an application requesting its approval in the U.S. was rejected in 2017. An office of the U.S. regulatory agency determined that PTC had failed to clearly demonstrate that the therapy was effective in DMD patients.