EMA agency continues to oppose renewing Translarna’s approval
CHMP stands by earlier opinions of therapy for DMD due to nonsense mutations
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The Committee for Medicinal Products for Human Use (CHMP) — part of the European Medicines Agency — again maintained its recommendation not to renew conditional marketing authorization for Translarna (ataluren), a treatment for Duchenne muscular dystrophy (DMD) caused by nonsense mutations.
The European Commission, which has final say over medication approvals in the European Union, is expected to issue a final determination in about two months. The therapy’s maker, PTC Therapeutics, is committed to keeping Translarna available in the meantime.
“As Translarna will remain authorized in Europe pending review by the European Commission, we will continue to ensure Translarna is available to boys and young men living with nonsense mutation Duchenne muscular dystrophy,” Matthew B. Klein, MD, CEO of PTC, said in a company press release.
PTC, Klein added, will “ensure the [European Commission] has all possible evidence to support continued authorization.”
Translarna in Europe was approved for eligible DMD patients in July 2014
DMD is caused by mutations in the gene that provides instructions to make dystrophin, a protein that’s critical for muscle function. Lacking dystrophin, DMD hallmark symptoms of muscle weakness and wasting progress. Since the dystrophin gene is located on the sex-determining X chromosome, the disease mainly affects boys and men.
In up to about 1 in 7 DMD patients, the disorder is caused by a nonsense mutation. This is a specific type of mutation in which a “stop” signal is erroneously put in the middle of the gene, a bit like having a stray period in the middle of a sentence. Translarna is designed to allow cells to read through the erroneous stop signal to produce a full-length version of the dystrophin protein.
Translarna was conditionally authorized in Europe about a decade ago to treat nonsense-mediated DMD in patients ages 5 and older who are able to walk. That conditional approval later was extended to individuals as young as 2 years old.
About a year ago, the CHMP issued a negative opinion recommending that Translarna’s conditional approval not be renewed, which would effectively pull it from the market. It was based mainly on data from the Phase 3 clinical trial Study 041 (NCT03179631), which tested the therapy against a placebo in boys with nonsense-mediated DMD ages 5 and older.
Study 041, according to the EMA, failed to demonstrate that Translarna was better than the placebo at preserving walking ability in patients who were experiencing a progressive loss of walking ability — the group that, theoretically, would show the clearest benefit if the medicine was working as intended. The regulatory agency also noted biomarker data that suggested Translarna’s effects on dystrophin production are modest at best.
But PTC has repeatedly argued that the totality of data available, including information from a real-world patient registry (NCT02369731), indicate that Translarna does offer some benefits for patients. After the initial 2023 recommendation, PTC asked the CHMP to reconsider, and the committee reaffirmed its negative opinion in January 2024.
Recent CHMP opinion reaffirmed that issued by the EMA agency in June
The opinion then was sent to the European Commission, which asked the EMA for an additional review taking into account newer real-world data. But the CHMP in June again recommended against renewing Translarna’s approval, saying that the further real-world data still fails to prove the medication actually works. PTC then again asked for a reconsideration, and now the agency again reaffirmed its negative recommendation.
PTC expressed frustration and disappointment with the reconsidered opinion. The company did not provided any further update on plans to seek U.S. Food and Drug Administration approval of the therapy for nonsense-mediated DMD, which it had announced earlier this year.
“CHMP again based its decision on the results of the primary analysis subpopulation of Study 041 instead of the totality of evidence for Translarna,” Klein said. “That evidence includes data across three placebo-controlled trials and our STRIDE registry that demonstrates consistent short and long-term efficacy as well as safety supportive of continued authorization. In addition, the CHMP opinion is clearly against the expressed wishes of physicians, patients and families throughout Europe.”
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