Is Eteplirsen reasonably likely to be considered for Accelerated Approval?

Posted by: Christine McSherry on April 15, 2013

In 2001, translating therapies into patients with Duchenne was only a dream.  Now, in 2013 it is becoming a reality.  Despite the challenges in drug development, we now see success in on several fronts, most notably with Sarepta’s lead compound, Eteplirsen.  In trial, Eteplirsen is demonstrating very encouraging results, and a crisp clean safety profile.  Eteplirsen is an “exon-skipping” compound that restores the genetic code (exon 51) and allows those with Duchenne, (amenable to 51), to produce a truncated version of the protein missing, dystrophin.  At 48 weeks, Sarepta announced that dystrophin as a surrogate endpoint had been achieved; functional data collected by the 6MW has shown stabilization of ambulation and suggests some gains as well.  Based on what we have seen, Eteplirsen appears reasonably likely to predict a real clinical benefit.

I have spent the last four months meeting with some of the highest-ranking regulatory officials in world.  I have been to Parliament to meet with the Shadow of Health Minister, Andy Burnham, MP, on several occasions. Additional European regulators attended our last meeting in early March of this year; Dr. Janice Soreth; FDA Europe Director liaison to EMA, Dr. Pavel Balabanov, Scientific Administrator; EMA, and John Johnston from the MHRA.

On a regular basis I have been meeting with officials at the FDA.  Multiple meetings with the Director of CDER; Dr. Janet Woodcock, Dr. Robert Temple, who serves as CDER’s Deputy Center Director for Clinical Science, Dr. Leonard Sachs from the Office of Medical Policy, Dr. Russell Katz the director of the Division of Neurology Products and the Commissioner of the FDA; Dr. Margaret Hamburg, where they all gave a firm commitment to stay focused on Duchenne and the sponsors providing treatment options.  They spoke in unification for seamless programs/trial designs that address the urgent unmet medical need in the rare disease space.  Repeatedly, they suggested that that the FDA does not want large Phase III placebo controlled trials when there is sound understanding of disease progression in fatal rare diseases. 

Their vision supports the plan outlined by Sarpeta’s CEO recently at WODC conference.  A plan that takes into consideration the shortened life span of those diagnosed with Duchenne and the subgroups that exist in the disease type, and meeting the known surrogate endpoint that is clearly the underlying cause of the disease, dystrophin. These novel ideas echo the sentiments that I heard, over and over again, by the regulatory agencies. 

There we have it, FDA, EMA, MHRA – all, wanting innovative trials meeting the unmet needs of a community, they want a population willing and wanting to take “permissible risk”. Now a company, a small biotech company, Sarepta Therapeutics is considering taking the risk for accelerated approval of Eteplirsen.

Is it reasonably likely?  

Given the fast progression of the disease, and the untimely death of these boys/young men with Duchenne, based on the safety and efficacy data released this far it would seem reasonably likely that Eteplirsen is an ideal compound to be considered for accelerated approval.



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