PTC Therapeutics Tanks After the FDA Denies DMD Drug Translarna Again

October 17, 2016
By Alex Keown, BioSpace.com Breaking News Staff

SOUTH PLAINFIELD, N.J. – Shares of PTC Therapeutics are down more than 30 percent this morning after the company announced the U.S. Food and Drug Administration once again denied the company’s drug, Translarna for the treatment of nonsense mutation Duchenne muscular dystrophy (nmDMD).

Translarna is a protein restoration therapy designed to enable the formation of a functioning protein in patients with genetic disorders caused by a nonsense mutation, according to PTC data. In February, the FDA issued a Refuse to File letter, which rejected PTC’s New Drug Application for Translarna. In the letter, the FDA said PTC’s application was “not sufficiently complete to permit a substantive review.” The company appealed the letter, but was notified that its first appeal of the refuse to file letter was denied by the FDA’s Office of Drug Evaluation I. PTC said it 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,” PTC said in a statement this morning.

PTC is calling for an advisory committee meeting that would allow clinical experts and representatives of the patient community to express their views on Translarna for the treatment of nmDMD.

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

Duchenne muscular dystrophy is an X-linked degenerative neuromuscular disorder causing severe progressive muscle loss and premature death. One of the most common fatal genetic disorders, DMD affects approximately one in every 3,500 boys born worldwide. DMD is associated with specific errors in the gene that codes for dystrophin, a protein that plays a key structural role in muscle fiber function. Progressive muscle weakness in the lower limbs spreads to the arms, neck and other areas. Eventually, increasing difficulty in breathing due to respiratory muscle dysfunction requires ventilation support, and cardiac dysfunction can lead to heart failure. The condition is universally fatal, and death usually occurs before the age of 30. The nonsense mutation is an alteration in the genetic code that prematurely halts the synthesis of an essential protein.

Getting a DMD treatment approved has been tough for many companies, as several have failed. However, in September Cambridge, Mass.-based Sarepta became the first to win approval of its DMD drug eteplirsen. Eteplirsen (Exondys 51) was approved under an accelerated approval pathway. When the drug was approved, BioSpace reported as part of the approval, Sarepta will need to conduct a two-year, randomized controlled trial to verify the drug’s benefits. At its core, more data is needed to prove that the drug actually improves motor functions. If that trial fails, FDA approval could be withdrawn.

Although PTC has been stymied in the U.S., Translarna is licensed in the European Economic Area (EEA) for the treatment of nonsense mutation Duchenne muscular dystrophy in ambulatory patients aged five years and older. The EMA reevaluated the drug and granted conditional approval based on “some evidence of effectiveness” and the fact that there was little if any alternative to the drug.

Shares of PTC Therapeutics are trading at $9.14 as of 12:08 p.m.