Sarepta and FDA agree plan for Muscular Dystrophy drug


Sarepta has overcome a major regulatory obstacle and now plans to file its Duchenne Muscular Dystrophy treatment with the FDA by the end of 2014.

The US company had received a major blow when the US regulator rejected its application in November, but a new plan agreed between the FDA and Sarepta has put it back on course.

Duchenne Muscular Dystrophy (DMD) is a rare degenerative disorder caused by a genetic defect, resulting in severe progressive muscle loss and premature death.

There are currently no treatments for the disease, which affects only boys, and the US company’s drug eteplirsen is currently the greatest hope for sufferers and their families.

The FDA ruled in November that the company’s main study, an analysis of the drug in just 12 boys, did not provide sufficient data for it to review for approval.

The study looked at the drug’s effect on the boys’ ability to walk, as well as their lung function, and also monitored levels of dystrophin, the key protein which helps maintain muscle function.

Sarepta says the trial showed marked responses in all these areas, but the FDA was unconvinced by the data, and had suggested a placebo-controlled trial could be required.

 Since then, it hasn’t been clear if the FDA’s reservations about the study could be overcome.  Now the company has announced that the regulator will accept the drug filing without a placebo controlled trial if other additional data is supplied.

The FDA says the drug could be reviewed under the Accelerated Approval pathway, which allows potential breakthrough drugs to be given priority review, but must provide proof of efficacy and safety once on the market, in the form of ‘confirmatory’ studies.

Based on the FDA’s guidance, Sarepta now plans to initiate several additional clinical studies with eteplirsen later this year in exon-51 amenable genotypes. These studies will include a trial with efficacy endpoints for ambulatory patients between the ages of 7 to 16 years who can walk a minimum distance, and two extra clinical trials to evaluate safety and biomarkers in DMD patients younger than seven years and DMD patients who have advanced in their disease progression to a point they cannot walk a minimum distance or can no longer walk at all.

Eteplirsen is an exon skipping drug, which tricks the body into skipping over one of the faulty gene codings which causes the disease. Eteplirsen skips exon 51 of the dystrophin gene, enabling the repair of specific genetic mutations that affect around 13% of the total DMD population.

 The FDA has now also urged Sarepta to begin clinical trials of back up or ‘follow on’ drugs in the same class, but targeted at another faulty exons.  This could help provide comparisons with eteplirsen in terms of safety and efficacy, which would reassure the regulator.

Clinical trials to start soon

“We are very pleased with the detailed guidance that the FDA has provided us on a potential eteplirsen approval pathway and their support of a historically controlled eteplirsen confirmatory study,” said Chris Garabedian, president and chief executive of Sarepta Therapeutics. “We also appreciate that the FDA shares our urgency in dosing a broader base of eteplirsen patients and has encouraged us to begin the clinical programme with our follow-on exon-skipping drugs as soon as possible.”

The company also plans to initiate a placebo-controlled study with one or more of its follow-on drug candidates in the same class by the end of the year.

Sarepta plans to begin dosing in the new confirmatory study in the third quarter, with dosing in the additional trials (i.e., younger and more advanced DMD patients) to begin later this year.  Detailed study eligibility criteria and clinical site information will be posted on and Let’s Skip Ahead, an online resource centre from Sarepta for the DMD community.

Patient activists

The nature of the disease means that it has one of the most dedicated set up patient activists. In the US, groups such as ‘The Race to Yes’ organised a petition calling for the FDA to find a solution to the problems, and claimed the new plan was a victory for their campaign.

"We have been waiting for this for a long time," said Tracy Seckler, whose son, Charley, has Duchenne. "This is good news that gives our children a fighting chance. But it's only one lap in a long race and we have a long way to go to get to the finish line. Too much time has already been lost, and in that time, boys have continued to get sicker and die.

"We know eteplirsen is safe and works. The children who have been treated for more than two years are clear evidence that the drug stabilises lung function and walking ability for the group amenable to this treatment."

Rival treatments

The news also gives new hope to other companies with DMD drugs in their pipelines.  Prosena has its own drug, drisapersen in development, but its trials failed to show improvement in walking ability in patients in September 2012.

Another pipeline treatment for the condition is being developed by UK-based firm Summit. Its drug is SMT C1100 and entered a phase 1b trial in patients with the condition in November 2013. Summit’s drug has a different mechanism of action, and works by increasing the utrophin protein, which could be a substitute for the missing dystrophin.



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Andrew McConaghie