PTC Therapeutics has been denied its first appeal contesting US regulators' refusal to accept the marketing application for Translarna as a treatment of nonsense mutation Duchenne muscular dystrophy (nmDMD).

In February the firm's stock was sent into a nosedive after the US Food and Drug Administration issued a Refusal to File letter for the oral, first-in-class, protein restoration therapy, on grounds that "the application was not sufficiently complete to permit a substantive review".

Translarna (ataluren), which is licensed in Europe for the treatment of patients aged five and above, is designed to enable the formation of a functioning protein in patients with genetic disorders caused by a nonsense mutation, an alteration in the genetic code that prematurely halts the synthesis of an essential protein.

Primarily affecting males, DMD is a progressive muscle disorder caused by the lack of functional dystrophin protein, which is critical to the structural stability of skeletal, diaphragm, and heart muscles. Patients with DMD lose the ability to walk as early as age 10 and experience life-threatening lung and heart complications in their late teens and twenties, and there is no approved treatment for the condition. It is estimated that nonsense mutations account for around 13% of DMD cases.

While a Phase III trial with Translarna published last Autumn failed to meet its primary endpoint of change from baseline in the six-minute walk test (6MWT) in the overall intent-to-treat study population, a highly significant benefit of 47 meters was demonstrated in the pre-specified patient population of 300m-400 meters at baseline.

PTC said it now intends to escalate its appeal to the next supervisory level of the FDA. "This is an iterative process and the company anticipates that multiple cycles of appeals to progressively higher levels of the FDA may be required," it said in a company release.

"We believe that fair consideration of the totality of Translarna's data requires a full review of our application by the FDA," noted Stuart Peltz, PTC' chief executive. "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."

The company also maintains its position that PTC should, "under existing law and in fairness to patients, be provided the same opportunity for full review that the [FDA's Division of Neurological Products] gave to other recent applicants for products in development for different subsets of the DMD population".