Ataluren (PTC124) for Duchenne-Becker MD related to premature stop codons did not receive approval in Europe prior to completion of an ongoing phase 3 trial
The experimental drug ataluren, in development for Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD) caused by specific mutations in the gene for the dystrophin protein, will not receive conditional approval at this time from the European Medicines Agency (EMA). Ataluren's developer is requesting that the EMA re-examine the data.
PTC Therapeutics, a New Jersey biopharmaceutical company that has been developing ataluren (formerly called PTC124) with support from MDA, announced the decision made by the European regulatory agency in a Jan. 24, 2014, press release. The company filed the conditional marketing application with the EMA in December 2012.
The drug is now in a phase 3 trial of 220 boys with nonsense mutation-related DMD or BMD who are 7 to 16 years old and meet other study criteria. The trial remains open to new participants. Conditional approval would have allowed the company to make the drug available to patients in Europe prior to the completion of the phase 3 trial, although full approval would still have required completion of this trial.
Results of the phase 3 trial are required for approval of ataluren by the U.S. Food and Drug Administration (FDA), regardless of what the EMA's final decision.
"While we appreciate that this delay is a disappointment for families living with this disorder, we are encouraged by the detailed discussions we have had with the EMA through this application process," said Stuart Peltz, CEO of PTC Therapeutics. "We understood and communicated that there was a substantial risk that the EMA would not grant us conditional approval when we began this process 15 months ago. However, we pursued this approach because we believe ataluren has shown a clinically meaningful benefit for nonsense-mutation DMD patients in our trials, has been generally well tolerated, and should be made available as soon as possible."
Ataluren — given by mouth — is known as a "stop codon read-through" drug, designed to coax cells to "read through" (ignore) erroneous codes in the genetic instructions that would otherwise cause the cells to stop protein molecules before the production process is complete. These erroneous codes, known as "premature stop codons," or "nonsense" mutations, in the dystrophin gene are the cause of DMD or BMD in approximately 13 percent of patients with these disorders.
In 2010, PTC announced that in a 48-week, phase 2 trial of ataluren, participants who were given the lower of two ataluren dosage levels walked farther in six minutes than those who took a higher dosage of ataluren or a placebo.