PTC Begins Submission of New Drug Application for DMD Stop Codon Read-Through Drug

PTC Therapeutics has begun submitting an application for U.S. approval of Translarna (ataluren) for Duchenne MD; completion of the application is slated for late 2015

Article Highlights:
  • Translarna (also known as ataluren and formerly as PTC124) is an experimental Duchenne muscular drug whose development MDA has long supported; the drug is designed to coax cells to ignore ("read through") erroneous, premature stop codes in the gene for the dystrophin protein so that functional dystrophin can be produced.
  • Conditional approval for Translarna was granted by regulatory authorities in the European Union in August 2014. 
  • U.S. approval will be contingent upon completion of an ongoing (but now closed), phase 3 trial of ataluren.
by Margaret Wahl on December 23, 2014 - 11:20am

New Jersey-based PTC Therapeutics has begun submitting a rolling new drug application (NDA) to the U.S. Food and Drug Administration (FDA) for the approval of its experimental drug for the treatment of Duchenne muscular dystrophy (DMD) caused by specific flaws (mutations) in the dystrophin gene. MDA has provided direct support to PTC Therapeutics for development of this drug, now known as Translarna, as well as support for laboratory research underlying its development.

In a Dec. 23, 2014, press release, PTC announced it had begun the process of an NDA submission to the FDA for Translarna (also known as ataluren and formerly known as PTC124) for the treatment of DMD in the approximately 13 percent of patients whose disease is caused by premature stop codon mutations in the gene for the muscle protein dystrophin.

Translarna is a stop codon read-through drug for DMD

Premature stop codon mutations, also known as nonsense mutations, cause cells to stop making a protein before genetic instructions have been completely "read." By utilizing a strategy known as stop codon read-through, the oral drug Translarna is designed to coax cells to ignore ("read through") erroneous stop codes in the dystrophin gene. It is hoped that stop codon read-through will allow full-length, functional dystrophin protein to be made and that the presence of functional dystrophin will improve muscle strength and function.  Dystrophin deficiency is the underlying cause of DMD.

MDA has long supported stop codon read-through as a strategy for DMD and has specifically supported the development of Translarna. PTC received a $1.5 million award from MDA in 2005 for development of the compound then known as PTC124. In addition, a basic research grant in 2003 from MDA to molecular biologist H. Lee Sweeney (see "Running a Stop Sign" section) at the University of Pennsylvania provided laboratory data foundational to this effort.

Conditional approval in Europe recently received; U.S. approval depends on phase 3 results

In August 2014, Translarna (ataluren) received conditional approval for the treatment of nonsense-mutation DMD in Europe. Conditional approval is a mechanism used by regulatory authorities in the European Union that allows patients with life-threatening disorders to gain access to an experimental drug before it is fully approved.

In the U.S., approval of Translarna is contingent on the results of a large-scale, phase 3 trial of Translarna.  This trial is ongoing but is no longer recruiting participants. PTC says it plans to finalize the NDA for Translarna in the U.S. in the fourth quarter of 2015, following the completion of this trial. In the meantime, a rolling submission to the FDA allows completed portions of an NDA to be submitted and reviewed on an ongoing basis.

"The initiation of our NDA submission for Translarna marks another signfiicant milestone towards providing Translarna to all nonsense-mutation Duchenne muscular dystrophy patients," said PTC CEO Stuart Peltz in the Dec. 23 announcement. "We look forwad to the completion of the ACT DMD confirmatory phase 3 clinical trial so that we can finalize the NDA. Gaining U.S. approval, in addition to Translarna's European approval, will help to make Translarna availalbe to patients across the globe. This is our commitment to the patients, families, advocacy groups and physicians who have worked and supported PTC Therapeutics through many years of research and development."








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