Cellular, Tissue and Gene Therapies Advisory Committee Meeting Presentation PDF
Preview Cellular, Tissue and Gene Therapies Advisory Committee Meeting Presentation
CO-1 Voretigene Neparvovec (Voretigene) for Confirmed Biallelic RPE65 Mutation- Associated Retinal Dystrophy October 12, 2017 Spark Therapeutics Cellular, Tissue and Gene Therapies Advisory Committee CO-2 Introduction Katherine High, MD President and Head of Research and Development Spark Therapeutics CO-3 Agenda Katherine High, MD Introduction President and Head of Research and Development Spark Therapeutics Mark Pennesi, MD, PhD Unmet Need Associate Professor in Ophthalmic Genetics Oregon Health and Science University (OHSU) Kathleen Reape, MD Efficacy Head of Clinical Research and Development Spark Therapeutics Deborah Kelly, MD Safety Head of Pharmacovigilance Spark Therapeutics Albert Maguire, MD Clinical Perspective Clinical Associate in Division of Pediatric Ophthalmology Children's Hospital of Philadelphia (CHOP) CO-4 Additional Experts Pre-clinical and clinical Jean Bennett, MD, PhD development programs University of Pennsylvania Community-based functional Duane Geruschat, PhD vision assessment Johns Hopkins University Chris Johnson, PhD Neuroscientist University of Iowa Steve Russell, MD Principal investigator University of Iowa Karmen Trzupek, MS, CGC Genetic counseling InformedDNA Julia Haller, MD Trial investigator Wills Eye Hospital Fan-Fan Yu, ScD Statistics Statistics Collaborative, Inc CO-5 Voretigene Neparvovec Subretinal Injection Improves functional vision and visual function in patients with biallelic RPE65 mutation-associated retinal dystrophy Progressive disease eventually leads to complete blindness in nearly all patients No treatment options CO-6 Voretigene Supplies Functional RPE65 Enzyme Resulting in Restoration of Visual Cycle CO-7 Voretigene Product: Adeno-Associated Viral Type 2 (AAV2) Gene Therapy Vector AAV2 efficiently transduces RPE cells AAV clinical experience for over two decades Drives expression of cDNA encoding human retinal pigment epithelium 65 kDa (RPE65) protein vg/mL: vector genomes per milliliter CO-8 Voretigene Manufacturing Results in Full Vector Particles Triple transfection of HEK293 cells Downstream purification process separates empty AAV capsids from full AAV capsids Essentially only full particles administered in final product Formulated in physiologic buffer containing surfactant to prevent loss of vector on product contact surfaces CO-9 Voretigene Dosing and Administration Sequential, bilateral, subretinal injection 1.5E11 vg in 0.3 mL total subretinal volume per eye Eyes administered 6 to 18 days apart Identify potential early-emergent surgical complications prior to second eye administration Reduces risk of immune response Injection location identified via imaging CO-10 Regulatory History Related to Evolving Understanding of RPE65 Mutation-Associated Retinal Dystrophy Year Action Orphan drug designation 2008 • Treatment of LCA due to RPE65 mutations Advisory Committee on cell and gene therapies for retinal 2011 disorders recommended novel endpoints for functional vision 2014 Breakthrough designation Orphan drug designation amendment 2016 • Treatment of IRD due to biallelic RPE65 mutations
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