First Appeal for FDA to Review Translarna Denied

TranslarnaPTC Therapeutics shared the latest news today on efforts to make its experimental drug Translarna available in the U.S. for the treatment of some forms of Duchenne muscular dystrophy (DMD). The company reported that the U.S. Food and Drug Administration (FDA) has denied its first appeal that a New Drug Application for Translarna be accepted and that the FDA conduct a full review of the drug.

PTC completed submission of its NDA to market Translarna in the U.S. in January 2016, but in February received a Refuse to File letter from the FDA stating that the application was not sufficient to permit a review. PTC submitted an appeal in July to escalate continuing discussions with the FDA about a path toward approval for the drug.

The company’s appeal was submitted to the next level of FDA management via the formal dispute regulation process. This process exists to encourage open, prompt discussion of scientific and procedural disputes that arise during the drug development process between FDA and companies. Within the dispute resolution process, PTC has said it is willing to consider multiple pathways to advance a potential FDA approval for Translarna, including the possibility of conducting an additional clinical trial under accelerated approval.

PTC now says it intends to escalate its appeal to the next supervisory level of the FDA as part of a process that may include multiple cycles of appeals to progressively higher levels of the regulatory agency.

A ‘read-through’ strategy

Translarna is under development by PTC to treat DMD caused by a type of genetic mutation known as a “nonsense mutation” or “premature stop codon.” This type of mutation results in production of a protein that is not complete and therefore not functional.

A “read-through” drug, Translarna is designed to act by changing the way muscle cells interpret genetic information, coaxing them to produce a needed muscle protein called dystrophin despite the presence of a nonsense mutation in the dystrophin gene. The drug, which is taken by mouth, may help approximately 13 percent of people with DMD. (Eteplirsen, also known as Exondys 51, recently received accelerated approval by the FDA and, similarly, may benefit approximately 13 percent of boys with DMD; however, the forms of DMD that are targeted by these two treatments are different.)

Developments to date

In October 2015, PTC announced results from its phase 3 “ACT DMD” clinical trial of Translarna, which demonstrated that although the drug failed to meet its primary endpoint, it was associated with statistically significant improvements to several clinical outcome measures for Translarna-treated patients. Analysis indicated the drug may slow functional decline in DMD patients, with some patients apparently responding more robustly to treatment than others.

In addition to having funded foundational work in DMD, MDA has contributed nearly $3 million towards Translarna’s development and phase 2 clinical testing.

Translarna received “conditional approval” in the European Union in August 2014 for use in people with DMD caused by a nonsense mutation who are at least 5 years old and able to walk.