Shooting for early OK, Sarepta lays out promising 3-year data on Duchenne drug

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Sarepta CEO Chris Garabedian

Coming up on the third anniversary of the Phase II trial launch for the Duchenne muscular dystrophy drug eteplirsen, Sarepta Therapeutics ($SRPT) says the small group of boys in the study continues to do well, underscoring the company's hopes for gaining an accelerated approval for this treatment as regulators appear to be changing their stance on early OKs. But rattled by signs that the boys in the study are registering a drop in their ability to walk over time, investors were in a punishing mood this morning, forcing a sharp drop in Sarepta's share price. 

At week 144 of the extension study, investigators say they've tracked a decline in 6-minute walk tests of 33.2 meters, offering up a significantly improved performance over the boys who were given a placebo in the first 6 months before switching to eteplirsen. There were no big stunners in the results, and that's an advantage for Sarepta.

"The surprise is how well these boys are continuing to hold up and maintain ambulation and really behave differently than anything suggested by natural history or any studies done in Duchenne muscular dystrophy," Chris Garabedian, the CEO at Sarepta, tells FierceBiotech.

Despite the company's take on the data, Sarepta's shares plunged 26% this morning as analysts chewed over the decline in walking distance as well as a skeptical take from Forbes' Matthew Herper, who's raised doubts before about the biotech's data from their small study. In his conversation with FierceBiotech ahead of the release, Garabedian responded to a query about the decline by noting that the drug is not a cure but promises to do better when applied earlier in the course of the disease, partially repairing the body's ability to generate dystrophin.

In addition to the walking tests, a classic measure of efficacy for DMD, investigators have also been tracking improvements on two key measures of respiratory muscle function and another goal line on lung volume.

Eteplirsen is one of three closely watched DMD drugs in the clinic, competing against therapies from Prosensa and PTC in a field which has seen some remarkable ups and downs over the last year. Sarepta's stock swelled to record highs on speculation that eteplirsen could win an accelerated approval at the FDA based on data from their tiny study. That proposition attracted plenty of long and short bets, which helped trigger a gyration in the stock price after Garabedian first dashed hopes of a quick OK, then raised them with the news that the FDA had provided guidance laying out how it could achieve its quest.

In this latest data set, investigators noted that at Week 144, "patients in the 30 mg/kg and 50 mg/kg eteplirsen cohorts who were able to perform the 6MWT (modified Intent-to-Treat or mITT population; n=6) experienced a decline of 33.2 meters, or about 8.5 percent, from baseline in walking ability. A statistically significant treatment benefit of 75.1 meters (p≤0.004) was observed for the mITT (intent to treat) population compared with the placebo/delayed-treatment cohort (n=4), which initiated treatment at Week 25 following 24 weeks of placebo. After experiencing a substantial decline of 68.4 meters from baseline to Week 36, the placebo/delayed-treatment cohort demonstrated a decline of 39.0 meters in walking ability from Week 36 through Week 144, the period from which meaningful levels of dystrophin were likely produced."

Now Sarepta plans to use its data from the extension study--as it launches new trials this quarter among a much-expanded group of boys--to persuade regulators that they should green-light this drug for marketing, ahead of the confirmatory study. 

That's a tall order, but this is a field where all the biotechs and patients involved have been on one of the wildest roller-coaster rides in the business.

Prosensa recently said it would shoot for an accelerated approval of its own, relying on new analysis and extension data, even though drisapersen failed in Phase III and GlaxoSmithKline ($GSK) bowed out as a partner. And PTC astounded just about everyone after European regulators reversed itself on some harsh criticism for its DMD drug, which also failed in a clinical study, and endorsed its quest for a conditional OK.

The ups and downs suggest that regulators on both sides of the Atlantic may be altering their views on DMD drug research to allow for quicker OKs. And if that's true, the change could have monumental consequences for drug developers racing to gain marketing approvals for the first drugs for DMD.

"I think what you're seeing is a recognition from regulators in Europe and the U.S.--with recent guidance for us and others--that they're understanding the risk/benefit of this disease," Garabedian says. "With no approved drugs they will consider more flexible pathways."

Garabedian has been steadily growing his Cambridge, MA-based company in anticipation of a launch. The roster of full-timers has expanded to 170, with about 25 more job openings.

- here's the release

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