Oct 2014 FDA:
FDA has expressed willingness to conduct a “rolling review” of Sarepta’s NDA. Under a rolling review, companies can submit, and FDA can review, portions of an application as they are completed. Once submission of all components is complete, the review clock begins. FDA expects the NDA for eteplirsen will qualify for a priority review.
FDA also plans to present the NDA for eteplirsen to a public advisory committee meeting before making a decision on approval. This will afford FDA the ability to gain advice from outside experts and interested stakeholders on the adequacy of the data to support approval, including the possibility of “accelerated approval” – a mechanism to approve drugs in particular situations prior to the availability of definitive evidence of effectiveness.
Based on minutes from a Type B Pre-NDA meeting held in September, the FDA has informed Sarepta that the following additional information should be included in their NDA submission for eteplirsen:
"The sponsor should include 3-month data from at least 12 to 24 newly exposed patients at the time the NDA is submitted."
"Available data from the other patients enrolled in the new eteplirsen studies (studies 301, 203, 204) should also be included at the time the NDA is submitted, even if exposure is less than 3 months in duration."
"Additional data from later time points and from newly enrolled patients should be submitted in the 120-Day Safety Update."
"FDA strongly advises the sponsor to obtain and submit patient-level natural history data. FDA is prepared to appeal to the academic groups holding the data to allow the sponsor a means to acquire the data."
"The study 201/202 clinical site inspection conducted in May, 2014, after the issuance of the April 15, 2014, guidance letter, uncovered marked disparities in the immunohistochemistry methodology and concerns about the reproducibility of the data. The lack of confirmation of robust dystrophin measurement during the site visit necessitates including the independent assessment of dystrophin-positive fibers and 168-week efficacy data from study 201/202 in the NDA."
Pat Furlong, Founding President and CEO of Parent Project Muscular Dystrophy (PPMD), a nonprofit organization focused on finding a cure for Duchenne muscular dystrophy said, “PPMD’s benefit-risk pilot data demonstrated that parents’ highest priority is to slow DMD progression. With this priority in mind, these Phase II data have exceeded our expectations”. “In practical terms, continued ambulation and preservation of respiratory function have immense benefit for individuals with Duchenne. It is important to keep in mind, that individuals participating in this study lived with Duchenne for over 9 years on average prior to receiving eteplirsen, an age when the pathological process that occurs based on the absence of dystrophin is typically well underway. Understanding this, in the eyes of the community these Phase II data are significant and represent an important step toward changing the landscape.”