Cellular, Tissue and Gene Therapies Advisory Committee Meeting Presentation

119 Pages·2017·8.49 MB·English

by  Spark Therapeutics

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