In a damning indictment, FDA review scorns PTC’s Duchenne drug for repeated failures

PTC Therapeutics $PTCT exec team proved this week that they are gluttons for punishment.

PTC Therapeutics CEO Stuart Peltz

After enduring two humiliating slap-downs at the FDA for their would-be Duchenne drug ataluren, the biotech — led by CEO Stuart Peltz — has forced the agency’s hand, requiring a panel review on Thursday. And in the agency’s review of the drug, released Tuesday morning, the FDA went to considerable lengths to explain why they think this drug — provided an accelerated approval in Europe, where it’s sold to patients as Translarna — has repeatedly proved to be unworthy of an approval.

PTC shares slid 23% after the review landed, proving that there are still clear lines on efficacy that the FDA will not cross.

The summary says it all. Regulators at the FDA reiterated a series of damning conclusions, with no positive data to consider. PTC’s post hoc analyses of failed studies, they concluded, are unconvincing in light of the fact that the results were “clearly negative”, while highlighting the “misleading nature of exploratory analyses of negative trials.” And there’s no reason to believe that any future trials of this drug will prove it can be effective.

In full, the FDA stated:

Ultimately, no positive results from any prospectively planned analyses that are persuasive have been provided with this application. The applicant has presented only the results from numerous post hoc and exploratory analyses that are intended to mitigate two negative clinical trials. In 2011, the applicant claimed that the effectiveness of ataluren had been established based on the post hoc analyses of the ADP population in Study 007. However, when this conclusion was prospectively evaluated in Study 020, the results were clearly negative. This finding directly highlights the frequently misleading nature of exploratory analyses of negative trials. It is arguable that some trends observed in the applicant’s data may warrant further prospective investigation, which the Agency has consistently encouraged the applicant to consider. Even so, for the reasons discussed above, it seems quite possible that any future study designed based on exploratory analyses of Study 020 will also turn out to be negative, just as Study 020, which was based on exploratory post hoc analyses from Study 007, was negative. The analogous results from the applicant’s development of ataluren for the treatment of nmCF offer a similar cautionary tale. Overall, the data intended by the applicant to establish the effectiveness of ataluren for the treatment of nmDMD are not persuasive.

That qualifies as one of the most conclusive rejections I’ve seen of any drug application at the FDA. Possibly PTC was emboldened by the agency’s accelerated OK of Sarepta’s drug, even though the company never provided data that the drug could work. In this case, though, the agency feels they have plenty of data to conclude that ataluren doesn’t work. And there’s no evidence to suggest that Janet Woodcock will be riding to PTC’s defense. Even a big showing of support from Duchenne parents Thursday may prove unlikely to tip the scales in PTC’s favor.

PTC, though, continues to push ahead in DMD, regardless of the criticism that has been leveled against it. That was proved again after the company bought out  a cheap, old European steroid — deflazacort — from Marathon Pharmaceuticals after Marathon execs decided to bag it and flee from the intense reaction to their plans to price it at $89,000 list after gaining the agency’s OK. PTC is now selling deflazacort at an even higher rate for some of the older, larger boys suffering from DMD after parents had been able to source it abroad for about $1,000 a year.

European regulators have repeatedly given PTC a pass with their drug. And there’s no indication that even a damning response like this will change their position.

The best place to read Endpoints News? In your inbox.

Comprehensive daily news report for those who discover, develop, and market drugs. Join 47,700+ biopharma pros who read Endpoints News by email every day.

Free Subscription

Research Scientist - Immunology
Recursion Pharmaceuticals Salt Lake City, UT
Director of Operations
Atlas Venture Cambridge, MA

Visit Endpoints Careers ->