FDA panel pans PTC’s post hoc pitch, shredding DMD dream

Most of the FDA panel said the data presented by PTC were inconclusive.

A panel of experts convened by the FDA has overwhelmingly knocked back PTC Therapeutics’ filing for approval of ataluren. The experts panned PTC for relying on post hoc analyses, not all of which were convincing, to make its case for approving the Duchenne muscular dystrophy (DMD) drug.

Asked if the data show the drug is effective, ineffective or are inconclusive, 10 of the 11 panelists told PTC to come back with more compelling evidence. While none of the panel wrote off ataluren as a total no-hoper, the fact most of the experts saw the current evidence as weak suggests PTC’s pitch for approval is unlikely to succeed.  

PTC pushed through to an advisory committee meeting despite ataluren having come up short in two clinical trials. The FDA refused to review applications from PTC following both clinical missteps. But, with the success of Sarepta Therapeutics still fresh in the memory, PTC forced the issue and got its day at the FDA.


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That introduced public testimonies into the mix. But, although many of the experts said the stories were compelling, these emotive aspects played second fiddle to concerns about the data in their assessments.  

“The critical issue is ... when the studies were set up and evaluated prospectively there was not a clear effect. Then retrospectively it looked like there were certain areas where there were clear effects. That kind of reanalysis can be very misleading,” Aaron Kesselheim, M.D., associate professor of medicine at Harvard Medical School, said.

Other experts also pointed to PTC’s reliance on post hoc data dives and subgroup meta analyses to cover for its prospective failures as leaving ample scope to doubt whether the drug works.

If the FDA follows the panel’s lead and knocks back PTC, the biotech will need to bolster its case with prospective clinical data before making another run at the agency. Many of the panelists encouraged PTC to have another crack and showed that, although backing the current filing would mean bending too far, they are flexible. 

“I understand defining an acceptable significance level in this study is a bit of a sliding scale, a bit of a value judgement, and I think it’s reasonable to alter it,” Icahn School of Medicine’s Mark Green, M.D., said. “So I hope as we go forward ... with this drug development that we predefine these significance levels before the data is broken,” 

Green called the data presented by PTC “disappointing.” 

Shares in PTC rose 10% in after-hours trading, showing the extent to which the FDA’s internal savaging of the filing had beaten down already low expectations. In that context, the “not now, maybe next time” message that emerged from the panel was more upbeat than might have been expected, although it is debatable whether further investment in ataluren is a good use of R&D dollars.

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