PTC Therapeutics Tight Lipped on Clinical Data; Investigator Speaks Out

Wow. A drug company actually downplaying its phase 2 data?

That's the charge of child neurologist Brenda Wong, an on-site investigator of PTC Therapeutic's ataluren (or PTC124) in muscular dystrophy, according to a report at MedPage Today.

Last month, PTC Therapeutics and its collaborator Genzyme announced that a treatment-related change in the primary endpoint, the 6-minute walk test, of a phase 2b trial of ataluren in Duchenne or Becker muscular dystrophy* (nmDBMD) did not reach statistical significance at 48 weeks. However, Wong, speaking at the just-completed annual meeting of the American Academy of Neurology in Toronto, said that patients treated with ataluren in the phase 2 trial experienced a mean improvement of 29 meters in the 6-minute walk test—which was just shy of the trial's prespecified target of 30 meters. This detail and others were not provided by PTC in its official communication.

Wong also said that the endpoint difference between ataluren- and placebo-treated patients was significant, when a different statistical test (a ranked analysis of covariance) was used, instead of what was prespecified (a simple analysis). Another important outcome: low-dose ataluren was more effective at delaying a deterioration in mobility than high-dose ataluren—which was no better than placebo. Wong proposed that low-dose ataluren may be more effective, because it has a relatively moderate effect on ribosomal activity. (Ataluren is designed to cause ribosomes to ignore a premature stop codon during protein translation.)

It's speculation here, but PTC may be reticent to broadcast details of its trial results, owing to the legal troubles it encountered in Gunvalson v. PTC Therapeutics in 2008 and the resultant threat to its clinical-trial program. In this legal case, which was correctly reversed on appeal (in favor of the company), a boy with nmDBMD demanded compassionate access to the drug outside of an ongoing clinical trial.

According to the NIH database, ataluren is currently being studied at the phase 2/3 level in cystic fibrosis and hemophilia A and B (in cases on nonsense mutations). Phase 3 trials in muscular dystrophy are not listed.

* Due to a nonsense (or premature stop codon) mutation, not a more common deletion mutation.