Sarepta Therapeutics Announces Regulatory Update on New Drug Application Submission for the Approval of Eteplirsen for the Treatment of Duchenne Muscular Dystrophy
Oct 27 14
Sarepta Therapeutics, Inc. provided an update on its discussions with the U.S. Food and Drug Administration (FDA) regarding its planned new drug application (NDA) submission for the approval of eteplirsen for the treatment of Duchenne muscular dystrophy (DMD). In meeting minutes received last week from a Type B Pre-NDA meeting that took place in September 2014, the FDA provided updated guidance regarding the specific data to be included as part of, or at the time of, Sarepta's NDA submission. The guidance states that additional data are now required as part of the NDA submission including the results from an independent assessment of dystrophin images and the 168-week clinical data from study 202. Additionally, the guidance requests more specific data including a minimum duration of safety in new patients exposed to eteplirsen, patient-level natural history data to be obtained by Sarepta from independent academic institutions, and MRI data from a recent study conducted by an independent academic group. The FDA indicated that further discussion with Sarepta will be necessary to determine what would constitute a complete NDA. Based on these requests, Sarepta plans to submit an NDA by mid-year 2015, pending any additional requests from further discussions with the FDA. The company announced that it is committed to satisfying the FDA's updated requests for these specific data to be included as part of an NDA submission and will continue to work with the Agency toward the goal of a complete and acceptable NDA filing. The company expects that all of the data requests and additional FDA discussions that have currently been outlined can be completed in time for an NDA submission by mid-year 2015. Obtaining an FDA approval of eteplirsen for the DMD patients who may benefit from the drug continues to be the company’s higher priority. 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. 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.
Sarepta Therapeutics, Inc. - Special Call
Oct 27 14
To provide an update on its discussions with the U.S. Food and Drug Administration regarding its planned New Drug Application submission for the approval of eteplirsen for the treatment of Duchenne muscular dystrophy (DMD)
Sarepta Therapeutics, Inc. Announces Publication of Ebola and Marburg Phase I Clinical Study Results in Antimicrobial Agents and Chemotherapy
Oct 16 14
Sarepta Therapeutics, Inc. announced the publication of results from two single ascending-dose studies that demonstrated no clinical or toxicologic safety concerns with the company's drug candidates for the treatment of Ebola and Marburg virus, respectively. The study results are to be published in the November issue of the American Society for Microbiology's journal, Antimicrobial Agents and Chemotherapy and are available online at dx.doi.org/10.1128/AAC.03442-14. AVI-6002 for the treatment of Ebola is a combination therapy of two phosphorodiamidate morpholino oligomers (PMOs AVI-7537 and AVI-7539), which target the viral matrix proteins VP24 and VP35, respectively. AVI-6003 for the treatment of Marburg is a combination therapy of two PMOs, (AVI-7287 and AVI-7288), which target the viral proteins VP24 and NP, respectively. These drug candidates use Sarepta's advanced and proprietary PMOplus(R) chemistry, which is also the basis of the company's clinical-stage influenza drug candidate, AVI-7100. Results from previous viral challenge studies of AVI-6002 and AVI-6003 in non-human primates demonstrated prevention of disease development and death following exposure to Ebola or Marburg virus. Subsequent animal studies demonstrated that for each combination therapy, only one oligomer contributed to efficacy, and therefore, the lead drug candidates for Ebola and Marburg have since become the single compounds AVI-7537 and AVI-7288. The two Phase I clinical studies were randomized, double-blind, placebo-controlled trials designed to characterize the safety, tolerability and pharmacokinetics of single doses of intravenous formulations of AVI-6002 or AVI-6003 in healthy adult volunteers. In each study, 30 subjects were enrolled in six cohorts receiving up to 9 mg/kg of the combination drug candidates (4 active:1 placebo per cohort) for a total of 60 subjects. Results showed the compounds to be well-tolerated with no dose limiting level demonstrated. No clinically significant or dose-dependent effects were observed at any of the safety endpoints evaluated. The safety and pharmacokinetics of the four PMOplus(R) compounds comprising the two combination therapies were similar, regardless of the target RNA sequence.