PTC Therapeutics ($PTCT) can’t get the FDA to consider its Duchenne muscular dystrophy candidate Translarna (ataluren). The agency has denied the New Jersey company’s appeal of a refuse-to-file letter that dates back to February. The small cap shed about 20% in premarket trading on the news.
The company will continue its appeal to the next level within the FDA; it noted in a statement that it expects that “multiple cycles of appeals to progressively higher levels of the FDA may be required.”
PTC likely feels emboldened to make its case in light of the regulatory success of DMD peer Sarepta Therapeutics, which won FDA approval for its Exondys 51 (eteplirsen) last month, despite not having demonstrated any efficacy beyond a biomarker measure.
On an August earnings call, PTC CEO Stuart Peltz had this to say about the company’s FDA efforts: “We couldn't disagree more strongly or be more frustrated with the FDA's refusal-to-file letter concerning Translarna. We believe that Translarna not only meets the FDA standards with respecting to filing, but also includes adequate information to conclude that Translarna does not have the potential for abuse.”
He concluded, “We believe that Translarna provides a clinically meaningful benefit and has been helping United States boys and young men with Duchenne muscular dystrophy for years through our extension trial.”
A Phase III study did not meet the primary endpoint of change from baseline in the 6-minute walk test (6MWT) demonstrated a 15-meter benefit. But a prespecified combined meta-analysis of Phase III and Phase IIb data did find statistically significant benefits for Translarna across primary and secondary endpoints.
Translarna is designed to enable functional protein formation in patients with genetic disorders caused by a nonsense mutation. It’s already approved in Europe--where the notoriously tight-fisted U.K. agency NICE has already agreed to pay for it--but that requires an annual renewal process. As part of that, the European agency recently requested supplemental information including a major objection to the risk-benefit profile of Translarna. The company expects a decision on the renewal request in Europe before the end of this year.
In the U.S., PTC said it wants an advisory committee meeting that can fully assess Translarna as a treatment for nonsense mutation Duchenne muscular dystrophy (nmDMD). The company said that it believes the candidate is the only one in clinical development to address the underlying cause of nmDMD.
"We believe that fair consideration of the totality of Translarna's data requires a full review of our application by the FDA," said Peltz in a statement. "In light of this, continuing the formal dispute resolution process reflects our ongoing commitment to work with regulators and the Duchenne community to make Translarna available to nmDMD patients in the United States."