PTC Unveils Mixed Duchenne Results, But Plots an FDA Filing

Xconomy New York — 

It’s a three-way race to produce the first drug for Duchenne muscular dystrophy in the U.S., and none of the competitors is sprinting to the finish.

PTC Therapeutics (NASDAQ: PTCT) of South Plainfield, NJ, said today that its drug ataluren (Translarna) failed to meet its primary goal in a 228-person Phase 3 trial. Yet PTC still believes the data it’s accumulated present a compelling case to ask the FDA for approval.

The drug helped boys with Duchenne walk an average of 15 meters farther than those on a placebo on the standard six-minute walk test after 48 weeks, but the difference wasn’t statistically significant.

PTC contends that in patients who had been able to walk between 300 and 400 meters at the start of the study—47 in all—the drug succeeded. These patients had a 47 meter benefit after 48 weeks, the results were statistically significant, and further, all 47 patients were able to walk at the end of the study, whereas 4 of the 52 on a placebo lost that ability.

PTC also cited a pre-specified, combined look at the Phase 3 and an earlier, mid-stage trial and said taken together, the drug showed a statistically significant benefit for patients across a variety of primary and secondary measures.

The data paint an unclear picture. But given the state of care for Duchenne—it’s a crippling, degenerative muscle disease with no cure—the question is whether it’ll be enough for PTC nonetheless. Last year, after all, ataluren became the first drug approved—albeit conditionally—for Duchenne in Europe, three years after European regulators had originally rejected it in 2011.

PTC seems to be betting on more regulatory open-mindedness. Ataluren failed a mid-stage trial in the U.S., but PTC moved it into Phase 3 nonetheless, feeling that the earlier trial provided the necessary information to design a trial that would show the drug’s benefit. Those Phase 3 results came in this afternoon. With them, PTC now has two failed Duchenne trials on its hands.

PTC CEO Stuart Peltz said in a statement that “totality of the data” between its two placebo-controlled trials—this Phase 3, and the earlier mid-stage trial—show a “clinically relevant impact” on Duchenne patients. Because of that, PTC will charge ahead towards approval.

The company will submit the results to the EMA, and aims to wrap up an FDA application by the end of the year. By that time, an FDA advisory panel will already have made a decision on BioMarin Pharmaceutical’s (NASDAQ: BMRN) drisapersen. In January, another panel is scheduled to weigh in on Sarepta Therapeutics’s (NASDAQ: SRPT) eteplirsen.

Just like ataluren, drisapersen failed a Phase 3 trial, and BioMarin has also made the case that the totality of its data, combined with the severity of the disease, should support approval.

Investors initially sent shares down about 16 percent in after-hours trading Thursday, but they’ve since rallied and were up 8 percent after 6:30 pm ET.

Ataluren is designed to block the effects of so-called “nonsense mutations,” or single-point alterations in certain genes that stop patients from forming fully functioning versions of the proteins encoded by those genes. Only 10 to 15 percent of Duchenne cases stem from nonsense mutations. Sarepta and BioMarin’s drugs target a different group of Duchenne patients.