Research

PTC Therapeutics Escalates Discussions with FDA Over a Pathway to Approval for Ataluren to Treat DMD

Amy Madsen

PTC Therapeutics announced today that it recently has submitted an appeal to escalate continuing discussions with the U.S. Food and Drug Administration (FDA) about a path toward approval in the United States for Translarna to treat some forms of Duchenne muscular dystrophy (DMD).

PTC completed submission of its New Drug Application (NDA) to market Translarna in the U.S. in January, but in February received a Refuse to File letter from the FDA stating that the application was not sufficient to permit a substantive review.

The company submitted its recent appeal 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 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.

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.

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.

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.