PTC: With no evidence of Duchenne MD efficacy, FDA barred regulators' doors to ataluren

PTC Therapeutics CEO Stuart Peltz

PTC Therapeutics's new drug application for ataluren was gunned down because the company's back-to-back failed studies for the Duchenne muscular dystrophy drug didn't begin to meet the agency's standards on efficacy.

In a postmarket release tied to its annual numbers, the biotech spelled out the agency's refuse-to-file (RTF) letter, news of which gutted its stock price last week and left it scrambling to develop a follow-up plan.

Speculation over the content of the FDA's RTF notice has been buzzing in the days since the company stunned its investors with news of the reversal. PTC ($PTCT) acknowledged clearly that both studies had failed key endpoints on Duchenne MD when they were wrapped, but felt that they could make a case with regulators that controversial post hoc analysis on a subset group of patients did show a benefit.

But that argument failed to even make it far enough to warrant a formal review, let alone a panel discussion.

"PTC was notified in the letter that, in the view of the FDA, both the Phase 2b and ACT DMD trials were negative and do not provide substantial evidence of effectiveness," PTC stated. "The FDA also characterized certain of the company's adjustments to the ACT DMD study as post hoc and therefore not supportive of effectiveness. In addition, the FDA noted that the NDA did not contain adequate information regarding the abuse potential of Translarna, a requirement for new molecules that cross the blood-brain barrier. PTC is engaging in dialogue with the FDA to discuss and clarify the matters set forth in the letter and to determine the best path forward."

The FDA can hand out an RTF for a variety of reasons, including some very modest gaps in the information supplied or technical snafus on the application. To reject a drug due to its data, before the data are fully evaluated by regulators, is at the least an exceedingly rare event and may signal a shift in the FDA's stance on the initial NDA process, raising the bar on trial data. If so, that would be important to the industry.

At least one prominent analyst says the FDA's action will leave ataluren in limbo, unless the biotech chooses to mount a new Phase III study against tough odds.

"Our view is that this is the end of the road for ataluren in DMD in the US, unless PTCT wants to invest in running another trial," noted RBC's Simos Simeonidis. "Management "is engaging in dialogue with the FDA to discuss and clarify" the issues discussed in the RTF letter. Given the fact that the agency refused to even review the application, we consider highly unlikely that any sort of appeal has much of a chance to be successful in changing the agency's view."

Now that PTC has been barred, at least for now, from the FDA, the EMA is reconsidering its position on a drug that they handed an accelerated approval to in 2014. As of now PTC is still marketing their drug in a variety of European countries, even though the FDA says there's no reason at all to believe it can help patients.

Germany slashed the reimbursement price on the drug last week, and other regulatory agencies may respond as well.

This has been a harsh period for the handful of biotechs engaged in Duchenne MD work. BioMarin's ($BMRN) drug, drisapersen, was rejected as a flat failure, and Sarepta's ($SRPT) eteplirsen was given one of the harshest FDA reviews of recent times. Many patients and families, meanwhile, have been stunned by the agencies' hard line on Duchenne muscular dystrophy, a rare disease that first cripples and then kills its victims, with no available drugs to blunt its progress.

- here's the release

Read more on