approval (AA). Sarepta has made it clear that they intend to petition the FDA to allow the company to apply for AA and have a meeting with the FDA on this very topic scheduled shortly.
What are the conditions necessary to meet the requirements for AA? Sec 901 of FDAMA and FDAISA govern access to AA. Section 902 complements 901 by allowing expedited developement of ‘Breakthrough Therapies’ that benefits drugmakers by giving them frequent, prioritized access to FDA staff to help expedite the approval process.
Section 901 lays out three broad criteria that need to met in order to achieve AA status. The disease in question must be rare and life threatening. A surrogate endpoint needs to be identified that is reasonably likely to predict clinical benefits to prospective patients. And lastly, safety data is carefully weighed on a risk vs. benefit analysis, taking into account the needs and viewpoints of patients.
Section 902 works hand in hand with Section 901 by allowing a company access to FDA staff in order to ensure the most efficacious method to reach AA compliance. Importantly, Section 902 directs that clinical trials be both small and efficient (in the words of the statute “by minimizing the number of patients exposed to a potentially less efficacious treatment”)
It is clear to me that by all accounts a succesful treatment for Duchenne’s meets the criteria necessary to achieve AA. No one doubts that boys suffering from Duchenne’s are literally given a death sentence. While there are outlier cases of DMD patients living into their 50s, they are few and far between. Such standouts achieve extraordinary longevity through heroic usage of ventilators and other medical equipment leading to significant loss of quality of life. The sad fact is, the vast majority of DMD boys will not live to see their 30th birthday. There is currently no cure or treatment on the market that can change these grim statistics. In fact, it would not be far from the truth to say that a disease like Duchenne’s was the impetus for Congression action via FDAMA/FASIA in the first place.
It is also clear to me that the data on Eteplirsen meets the legislative intent of Section 901. The evidence linking the failure to properly express dystrophin mRNA with the deterioration of muscle is both widespread and without question accepted within the muscular dystrophy scientific community (This website maintained by UCLA is a good primer on this subject). Sarepta has proven the existence of dystrophin production in all 12 patients in the trial who received the drug – including the 4 placebo patients who subsequently went on treatment after week 24. Slides showing images from both the pre- and post-treatment cells taken from muscle biopsies are available on pages 12 & 13 of the January 2013 presentation. These images are stark examples of eteplirsen having the therapeutic effect of allowing the patient to manufacture dystrophic-positive fibers in the sarcolema (the membrane covering muscle fiber).
Without question, the safety data generated at trial was a home run when considered against the life-threatening nature of the illness. It’s not a stretch to say that of all the Section 901 hurdles, the safety profile of eteplirsen is the least worrisome of all.
The FDA is mandated to meet with a drug company developing a Section 902 Breakthrough Therapy in order to inquire as to Section 901 compliance within 60 days of requesting such a meeting (assuming the company in question meets all other statutory guidelines such as complete data submission, etc.) According to Sarepta’s CEO the request was made sometime in late December, so unless the FDA requested a short extension such a