FDA Requests More Trial Data for Translarna for DMD

PTC Therapeutics has been given a US Food and Drug Administration (FDA) Complete Response Letter (CRL) for investigational drug ataluren (Translarna) for nonsense mutation dystrophinopathies.

The New Drug Application (NDA) for Translarna as a dystrophinopathies therapy was yielded, according to PTC Therapeutics, due to a lack of effectiveness evidenced in clinical trials. The CRL indicated additional adequate clinical trials, as well as “other nonclinical and CMC matters,” would be needed to be addressed for another NDA.

DMD, a fatal genetic neuromuscular disorder that leads to heart and respiratory failure in patients by their mid-twenties, is caused by nonsense mutation in about 13% of all patient cases. Patients progressively lose muscle strength from early childhood into adolescence due to a lack of function dystrophin protein.

Stuart W. Peltz, PhD, PTC Therapeutics chief executive officer, said the company is extremely disappointed for the DMD patient community and “strongly disagrees with the agency’s conclusions.”

"We believe that this decision fails to consider the benefit-risk of ataluren and the high unmet medical need,” Peltz said. “Therefore, we plan to file a formal dispute resolution request next week."

According to the company, PTC Therapeutics is in the process of addressing the unnamed clinical and CMC matters addressed in the CRL notice.

An FDA advisory board endorsed by a vote of 10 to 11 that the evidence supporting Translarna as a DMD treatment was inconclusive, in a meeting held last month. In its briefing documents, the board noted that the NDA held a “large number of exploratory analyses that lack interpretability and are often entirely based on unblended data.”

“Ultimately, no positive results from any prospectively planned analyses that are persuasive have been provided with this application,” the document reads.

A press release regarding the decision was made available.