After FDA setback, PTC Therapeutics' DMD drug Translarna faces possible market withdrawal in Europe

A “surprised and extremely disappointed” PTC Therapeutics is scrambling to keep its Duchenne muscular dystrophy therapy Translarna on the European market after a detrimental review.

The Committee for Medicinal Products for Human Use (CHMP), the drug review body at the European Medicines Agency, has refused to convert Translarna’s conditional marketing authorization into a full approval in nonsense mutation DMD, PTC said Friday.

PTC plans to challenge the decision, while Translarna (ataluren) remains on the market during the re-examination process. A second opinion is expected in January 2024, the company said. If the European Commission eventually adopts the negative review, PTC may have to pull Translarna from the market.

“We are surprised and extremely disappointed by the CHMP decision, given the well-established and favorable safety and efficacy profile of Translarna,” PTC CEO Matthew Klein, M.D., said in a statement.

The CHMP looked at Translarna’s data from the placebo-controlled Study 041, the same trial that the FDA recently said doesn’t provide enough evidence to support a new drug application re-submission.

Translarna gained a conditional nod in Europe in 2014 based on Study 007. Results from the phase 2b study favored Translarna against placebo on a six-minute walk test at week 48 of treatment, the primary endpoint of the trial. Both Study 007 and a following Study 020 didn’t produce statistically significant results on the walk test.

When the EMA renewed Translarna’s conditional clearance in 2017, PTC agreed to use data from a third trial, Study 041, to confirm the drug’s benefit-risk profile. Compared with the previous trials, Study 041 is larger, and its primary endpoint focuses on patients in whom Translarna had previously shown better performances.

Ironically, the trial once again missed statistical significance on the primary endpoint in the selected patient subgroup. But it did hit a technical “nominally statistically significant” bar in the overall enrolled patients.

Across the Atlantic, PTC has repeatedly tried to win over the FDA and got nothing but rejections, starting with a refusal to file letter in early 2016.

Armed with the new Study 041 data, PTC is gunning for a re-submission. But the FDA recently told the New Jersey drugmaker that the study didn’t have substantial efficacy data to support a filing. As a result, PTC is requesting a formal meeting with the FDA to review the “totality of data collected to date,” the company said in its quarterly filing last month.

Translarna is designed to help ribosomes read past a premature stop mechanism in mRNA, known as a nonsense mutation, thereby allowing for the production of a functional dystrophin protein for DMD patients. About 10% to 15% of individuals with DMD have a nonsense mutation, and Translarna is currently the only approved therapy available for these patients in Europe.

Besides the three clinical trials, PTC has analyzed real-world data from a registry called STRIDE, which includes 300 boys with an average treatment duration of about 5.5 years. During the EMA re-examination, “PTC will also address concerns raised regarding the robustness of the STRIDE data in supporting long-term treatment benefit,” the company said.

In a Friday note to clients, analysts at William Blair projected that PTC will likely be able to covince the CHMP to keep the conditional authorization on the condition that the company runs another placebo-controlled trial, just like it did back in 2017.

“In addition, we anticipate an increase in vocal support by physicians, patients, and patient advocates who could pressure their local representatives to reverse their vote given that there are no other approved therapies for these patients,” the William Blair team said.

In the second quarter, Translarna brought in $77 million in revenue, up 46% over the same period last year.

Editor's Note: The story was updated with comments from a William Blair note.