Developing Rare Disease Products: Lessons from Serepta and Biomarin  
​[Posted on: Thursday, October 20, 2016]

Last month’s approval of Sarepta’s drug for Duchenne Muscular Dystrophy (DMD) by FDA shook the regulated industry due to the extremely arbitrary nature of the FDA decision. The review of the summary basis of approval, which lists the data FDA relied on to approve this drug, would not help. So, should all developers of products for rare diseases employ Sarepta’s strategy of extreme public campaign to pressure FDA? We will soon find out if FDA’s Sarepta decision leads to appeals of past decisions or legal action. Sarepta’s drug was often compared to a similar drug being developed by Biomarin. Most analysts wrote Sarepta off when FDA rejected Biomarin’s DMD drug in January. Biomarin even withdrew its application at EMA when it became clear that EMA would reject its drug as well. Now Biomarin is considering appealing its FDA decision in light of FDA’s Sarepta decision. Sarepta’s drug, Exondys 51, was approved based on a surrogate endpoint, namely increase in the level of dystrophin over baseline but only 4 out of 12 subjects showed increase in the levels of the marker above the mean. The maximum increase was 1.33% of the normal dystrophin levels. It has been reported that at least 30% of the normal level of dystrophin is necessary to avoid the disease and much higher levels may be needed to reverse the disease. So, it is hard to imagine a biological response with the increase in dystrophin levels seen with Exondys 51 treatment. Biomarin also looked for increase in dystrophin levels after treatment and from the results posted on clinicaltrials.gov, it seems Biomarin observed some increase in this protein as well. Since full results are not available in public domain, it is hard to know how Biomarin’s results compare to those for Sarepta. Sarepta heavily involved patients and their families in the publicity campaign to create pressure on FDA. The FDA advisory committee meeting for Sarepta’s drug had multiple patients and their families make a very passionate case for the approval of the drug. It seems that strategy of using patients to plead for their product worked for Sarepta. From the FDAs internal documents, it is clear that the Center Director got highly swayed by the emotional case made by the patients to approve the product despite strong opposition from the reviewers. With FDA’s increase emphasis on patient perspectives, particularly for rare disease, the way to go is to involve patients in the clinical trial design and advocacy with FDA as early as possible and certainly close to the market approval application. Sarepta also applied for and received Accelerated Approval designation for its product with allowed it use surrogate markers for the NDA. It is hard to imagine that FDA will approve another product with similar flimsy data as Sarepta but we have all been proven wrong once with Sarepta, so we no longer bet on it. Patient advocacy is the name of the game.