The EMA agency continues to oppose Translarna for reapproval

The Committee for Medicinal Products for Human Use (CHMP) – part of the European Medicines Agency – again maintained its recommendation to grant the conditional marketing authorization for Translarna (ataluren), a treatment for Duchenne muscular dystrophy (DMD) caused by nonsense mutations , cannot be extended.

The European Commission, which has the final say on drug approvals in the European Union, is expected to make a final decision in about two months. The maker of the therapy, PTC Therapeutics, is doing everything it can to keep Translarna available in the meantime.

“As Translarna will remain authorized in Europe pending the European Commission’s review, we will continue to ensure Translarna is available to boys and young men living with the nonsense mutation Duchenne muscular dystrophy,” said Matthew B. Klein, MD, CEO of PTC. a company press release.

PTC, Klein added, will “ensure that the (European Commission) has all possible evidence to support continued authorization.”

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Translarna in Europe was approved in July 2014 for eligible DMD patients

DMD is caused by mutations in the gene that provides instructions for making dystrophin, a protein crucial for muscle function. In the absence of dystrophin, DMD are characteristic symptoms of muscle weakness and decline in progression. Because the dystrophin gene is located on the sex-determining X chromosome, the disease mainly affects boys and men.

In approximately 1 in 7 DMD patients, the condition is caused by a nonsense mutation. This is a specific type of mutation that incorrectly places a “stop” signal in the middle of the gene, somewhat like a stray period in the middle of a sentence. Translarna is designed to allow cells to read the erroneous stop signal to produce a full version of the dystrophin protein.

Translarna received conditional approval in Europe about a decade ago for the treatment of nonsense-mediated DMD in patients aged 5 years and older who can walk. That conditional approval was later extended to people aged two years and older.

About a year ago, the CHMP issued a negative opinion recommending not renewing Translarna’s conditional approval, effectively removing Translarna from the market. It was based primarily on data from the Phase 3 clinical trial Study 041 (NCT03179631), which tested the therapy against a placebo in boys aged 5 years and older with nonsense-mediated DMD.

Study 041, according to the EMA, failed to demonstrate that Translarna was better than placebo in preserving walking ability in patients who experienced progressive loss of walking ability – the group that would theoretically provide the clearest benefit if the drug worked as intended. The regulatory agency also noted that biomarker data indicated that Translarna’s effects on dystrophin production are modest at best.

But PTC has repeatedly argued that the totality of available data, including information from a practice-based patient registry (NCT02369731), indicates that Translarna does provide benefits to patients. After the initial 2023 recommendation, PTC asked the CHMP for a reconsideration, and the committee confirmed its negative opinion in January 2024.

The recent CHMP opinion reaffirmed the advice given by the EMA office in June

The opinion was then sent to the European Commission, which asked the EMA for an additional assessment, taking into account newer real-world data. But the CHMP again recommended in June not to renew the approval of Translarna, because further real-world data still does not prove that the drug really works. PTC then requested another reconsideration, and now the agency reaffirmed its negative recommendation.

PTC expressed its frustration and disappointment about the reconsidered advice. The company provided no further update on plans to seek U.S. Food and Drug Administration approval for the therapy for bullshit-mediated DMD, which it announced earlier this year.

“The CHMP again based its decision on the results from the primary analysis subpopulation of study 041 rather than on the body of evidence for Translarna,” Klein said. “That evidence includes data from three placebo-controlled trials and our STRIDE registry demonstrating consistent short- and long-term efficacy, as well as safety that supports continued authorization. Furthermore, the CHMP’s advice clearly conflicts with the expressed wishes of doctors, patients and families Europe.”