The PTC Therapeutics drug Translarna failed its confirmatory study in Duchenne muscular dystrophy. Analysts say the European Commission’s decision to not adopt the Committee on Medicinal Products for Human Use’s negative opinion on the drug is unusual, if not unprecedented.

By Frank VinluanA PTC Therapeutics drug that failed a confirmatory study in the rare muscle-wasting disorder Duchenne muscular dystrophy may remain on the market in Europe for now. Regulators there took the rare step of declining to adopt a recommendation opposing renewal of the product’s marketing authorization.
The PTC drug, Translarna, received conditional marketing authorization in 2014 based on Phase 2 data. The conditional nature of this pathway requires a company to seek annual renewals of the authorization until it generates the clinical data that supports a standard marketing authorization. In a placebo-controlled Phase 3 study, Translarna failed to achieve the main goal of showing a significant change according to a six-minute walk test.
The European Medicine Agency’s Committee on Medicinal Products for Human Use (CHMP) issued its final opinion in January, concluding that Translarna’s benefit was not confirmed and its marketing authorization should not be renewed. That recommendation then went to the European Commission to confirm the recommendation. The commission typically follows CHMP recommendations.
On Monday, Warren, New Jersey-based PTC announced the commission decided not to adopt the CHMP opinion. The company said the commission has returned the opinion for reevaluation, asking the committee “to further consider the totality of evidence, including data from patient registries and real-world evidence, in a revised opinion.” PTC added that the European Medicines Agency has informed the company that the scientific advisory group meeting held for the drug last fall as well as all procedural steps that followed will be considered invalid. That means information from the September meeting and a subsequent meeting in January cannot be considered by the CHMP in any future evaluation of Translarna.
In Duchenne muscular dystrophy, a type of mutation called a nonsense mutation stops a cell from completely expressing dystrophin, a key muscle protein. The dystrophin that is produced is not the full-length version of the protein, and is therefore unable to perform its function in muscles. Translarna is an oral small molecule designed to get the ribosome to read through the messenger RNA that contains the mutation, enabling production of full-length protein.
Duchenne patients have few treatment options. FDA-approved antisense oligonucleotides marketed by Sarepta Therapeutics and NS Pharma each address only certain Duchenne patient subgroups with particular genetic signatures. The Sarepta gene therapy Elevidys has accelerated FDA approval, but only for patients ages 4 and 5. The FDA’s March approval of Italfarmaco drug Duvyzat covers Duchenne patients age 6 and older regardless of genetic variant. This drug is still under regulatory review in Europe.
Translarna, discovered and developed by PTC, is approved in Europe, Russia, and Brazil for treating Duchenne patients age 2 and older. The drug is PTC’s largest wholly owned product, accounting for $355.8 million in sales in 2023, a 23% increase compared to the drug’s sales in the prior year. The FDA rejected PTC’s application for Translarna in 2017. Since then, PTC’s efforts to persuade the FDA with additional data, including the same Phase 3 results reviewed by its European counterpart, have been unsuccessful. PTC has FDA approval for a different PTC Duchenne drug called Emflaza, a corticosteroid whose approach of reducing inflammation is thought to help muscle function. Emflaza accounted for $255.1 million in revenue in 2023.
In a note sent to investors Monday, William Blair analyst Sami Corwin said the European Commission decision to not adopt the CHMP opinion and instead return the matter to the committee is unconventional and, to the firm’s knowledge, unprecedented.
“We believe the [commission’s] decision is likely reflective of intense backlash from physicians and patient advocates who have no other therapeutic options and view Translarna as a safe and effective treatment, which is further supported by Translarna’s strong quarter-over-quarter growth in fourth quarter 2023 and first quarter 2024 despite the CHMP’s negative opinion,” she said. “At this time, we are optimistic that the CHMP will return a positive opinion to renew Translarna’s conditional marketing authorization.”
PTC is voicing caution on Translarna’s prospects. In its announcement of the commission’s decision, the company said it is pausing 2024 revenue guidance due to the inability to accurately forecast sales of the Duchenne drug.
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