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FDA assigns breakthrough therapy designation to innovative gene therapy approach to nyctalopia (night blindness)

SPK-RPE65, a novel gene therapy undergoing development for the treatment of nyctalopia, has received “breakthrough therapy designation” from the FDA. The drug’s sponsor, Spark Therapeutics, Inc., of Philadelphia, Pennsylvania, made the announcement in a press release stating that, “Breakthrough therapy designation is intended to expedite the development and review of investigational therapies for serious or life-threatening conditions where initial clinical evidence demonstrates a significant improvement over existing therapies”. SPK-RPE65, understood to be the lead product for its sponsor, is enrolled in a pivotal phase 3 clinical trial for the treatment of inherited retinal dystrophies caused by mutations in the RPE65 gene. The company anticipate preliminary data in the second half of 2015 and, subject to positive results, submission of a Biologics Licensing Application (BLA) with the U.S. FDA in 2016.  SPK-RPE65 additionally holds orphan designation in the United States and European Union.


The phase 3 study, formally entitled “A Safety and Efficacy Study in Subjects With Leber Congenital Amaurosis (LCA) Using Adeno-Associated Viral Vector to Deliver the Gene for Human RPE65 to the Retinal Pigment Epithelium (RPE) [AAV2-hRPE65v2-301]” aims to recruit 24 subjects, aged three years or older. LCA is well characterized as an early onset severe form of inherited retinopathy, representing about 5% of inherited retinal degenerations. The disease may be caused by mutations in any one of up to 15 different genes, mostly expressed in photoreceptors or the RPE (retinal pigment epithelium).


Spark Therapeutics, spun out of the Children’s Hospital of Philadelphia (CHOP), launched two gene therapy programmes in late 2013, following a $50M capital commitment from the hospital. The company includes gene therapy pioneers Jean Bennett, M.D., Ph.D., J. Fraser Wright, Ph.D. and Katherine A. High, M.D., among its founders. Spark is expected to leverage the extensive expertise and assets developed by CHOP’s Centre for Cellular and Molecular Therapeutics (CCMT), built up over a decade of frontline research and development in translational and manufacturing activities focused on human gene therapy. Commenting on receipt of the breakthrough designation, Jeffrey D. Marrazzo, CEO of Spark Therapeutics stated, “FDA’s breakthrough therapy designation for SPK-RPE65 underscores the serious unmet medical needs faced by patients with genetic blinding conditions. We look forward to working closely with FDA to facilitate the review of SPK-RPE65 as we work to bring this potentially transformative treatment to patients”.