Prosensa to Begin Confirmatory Studies for Duchenne Muscular Dystrophy

James Radke

Today, Prosensa announced it is going ahead with its plans to pursue a New Drug Application (NDA) filing with the FDA for drisapersen to treat patients with Duchenne muscular dystrophy who would benefit from exon 51 skipping therapy (approximately 13% of total Duchenne population).  The company also announced it plans to seek an accelerated approval pathway based on existing data.

That is a bit surprising given that the most recent study failed to meet its primary endpoint

However, after analyzing the data further and obtaining guidance from the FDA, the company is confident they can now design the pivotal clinical trials necessary to gain approval.

In a press release, the company outlined the two studies that the FDA has proposed:
1.       "A historically-controlled trial might be acceptable to confirm clinical benefit following accelerated approval. We note that a historically-controlled study is likely to provide interpretable evidence of efficacy only if the beneficial effect of drisapersen is large, by clearly showing that performance is better in drisapersen-treated subjects than could be reasonably expected, based on knowledge of the natural history of the disease. The effect size would have to be sufficient to overcome the uncertainty inherent in historically controlled trials, and motivational factors that can affect the results.
2.       A randomized, placebo-controlled trial of another exon-skipping drug with a similar mechanism of action, directed at a different exon (e.g., PRO044 or PRO045), with demonstration of a correlation between dystrophin protein production and definitive clinical benefit on 6-minute walk or another measure, could provide confirmatory evidence of drisapersen's clinical benefit if approval were based on a surrogate endpoint."

In addition to those two studies, the company also announced it plans to redose those patients in the initial study that had to discontinue treatment earlier this year as the company re-evaluated its clinical strategy.  The company plans to redose those boys in the third quarter of 2014.   Whether some of those boys opt to switch to Sarepta’s clinical trial with its exon 51 skipping drug eteplirsen remains to be seen.

About Duchenne muscular dystrophy

Duchenne muscular dystrophy is a progressive muscle disorder caused by the lack of functional dystrophin protein. Patients with Duchenne muscular dystrophy lose the ability to walk as early as age 10 and experience life-threatening lung and heart complications in their late teens and twenties.

There are an estimated 35,000 patients with Duchenne in the United States and Europe but the population has many subsets based on mutations of the dystrophin gene.

Both Sarepta’s eteplirsen or Prosensa’s drisaperson should be effective in the same 13% of the Duchenne population who would benefit from exon 51 skipping  therapy (i.e., those with mutations near exon 51 of the dystrophin gene) while PTC Therapeutics’ ataluren should be effective in another 13% subset who have nonsense mutations in the dystrophin gene.

All three companies are starting, or have started, phase 3 confirmatory studies.

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