Déjà Vu for PTC as FDA Declines to Consider Duchenne Drug App

Two times, PTC Therapeutics has asked the FDA to look at an application to approve a Duchenne muscular dystrophy drug it’s been developing. And now two times, the agency has sent the South Plainfield, NJ-based company back to the drawing board.

This morning, PTC (NASDAQ: [[ticker:PTCT]]) announced that it’s received a “refuse to file” letter from the FDA, meaning the agency won’t even look at the application for its Duchenne drug prospect, ataluren (Translarna), in its current form.

According to a short statement from PTC, the FDA said its application “was not sufficiently complete to permit a substantive review.” The company is reviewing the letter “to determine the appropriate next steps.” Shares of PTC immediately plummeted more than 40 percent in pre-market trading on Tuesday morning.

This is the second time PTC has been hit with this type of news. In 2011, the company filed an application with the FDA to approve ataluren for a genetic subset of patients with Duchenne, a progressive, crippling disease with no cure or effective treatments. The agency rebuffed PTC’s efforts and sent a refuse to file letter, noting that the single placebo controlled study it had conducted to that point for ataluren had failed, according to regulatory filings from PTC.

Since that time, PTC has gone public and won conditional approval of ataluren in Europe in 2014—a first for the field. But the drug has continued to produce mixed results in clinical testing. In October, ataluren failed to meet its primary goal in a 228-person Phase 3 trial. PTC leaned on a pre-specified, combined look at the Phase 3 and an earlier study, arguing that taken together, the drug showed a statistically significant benefit for patients across a variety of measures.

CEO Stuart Peltz said in a statement at the time that the “totality of the data” between those two studies showed a “clinically relevant impact” on Duchenne patients. PTC charged ahead with a regulatory filing based on that notion.

This was a similar gamble to the one BioMarin Pharmaceutical (NASDAQ: [[ticker:BMRN]]) recently made on drisapersen, another experimental Duchenne drug. Drisapersen had failed a Phase 3 trial, but BioMarin similarly figured pooling data together would sway regulators to approve a drug for a disease with no effective treatments. The FDA agreed to look at the application, but ultimately rejected drisapersen in January, two months after its scientists skewered the data at an advisory panel meeting.

With the status of both ataluren and drisapersen in the U.S. now in limbo, all eyes turn to Cambridge, MA-based Sarepta Therapeutics (NASDAQ: [[ticker:SRPT]]), whose Duchenne drug, eteplirsen, the FDA is expected to rule on by the end of May. Sarepta has its own issues; the data it has submitted to the agency largely relies on a single, small trial. As with drisapersen, FDA scientists similarly took apart Sarepta’s data, sending shares tumbling downward. Whether that will lead to the same result as the others should be decided in a few months.