Retinal Degenerations

Transcription

1 Treatments and Clinical Trials for Retinal Degenerations Jacque Duncan, M.D. UCSF Kearn Family Center for the Study of Retinal Degeneration December 4, 2015 Financial Disclosures Grant Support Consultant/Scientific Advisory Board Foundation Fighting Blindness Foundation Fighting Blindness USFDA Office of Orphan Product Spark Therapeutics Development AGTC Lowy Medical Research Institute Shire Research to Prevent Blindness California Institute for The Claire Giannini Foundation Regenerative Medicine That Man May See, Inc. UC Irvine/jCyte Lawrence L Hillblom Foundation Ocugen Neurotech USA, Inc. Okuvision Sucampo AG ISIS Pharmaceuticals Retinal Degenerations Diverse group of inherited diseases All associated with progressive loss of photoreceptors Emerging technologies provide hope for patients with severe vision loss Recent Developments Treatments for Patients with Severe Vision Loss: Restore Vision Prosthetic Devices Stem Cells Cure the Problem: Gene Therapy 1

2 Visual Prosthetic Devices Bypass the missing photoreceptors Stimulate the retinal cells the photoreceptors talk to: bipolar and ganglion cells Identify position, orientation, motion of objects Identify windows, doorways Retinal Prostheses Subretinal Prostheses Epiretinal Prostheses Retina Implant AG TM Second Sight, Model I TM Retina Implant AG Alpha IMS System Second Sight Argus II System 3x3 mm 2 subretinal microchip 1,500 electrodes, no external camera July 3, 2013: CE Mark approval granted Clinical trial recruiting in Europe Humayun M et al, Ophthalmology 2012: 119;

3 Second Sight Argus II System FDA Approval 2/14/2013 March 2, 2011: CE Mark approval granted for Argus II System February 14, 2013: US FDA grants Humanitarian Use Device Exemption January 2014: first commercial devices implanted at University of Michigan Offering Argus II at UCSF: Contact Scott Miller to refer patients who are NLP due to RP at , fax Stem Cell Therapy Potential to restore vision that has been lost if stem cells are used to replace vision cells Current trial to prevent further vision loss in dry age-related macular degeneration and Stargardt disease by replacing RPE cells Clinical Trial at UCLA, BPEI, Mass Eye and Ear, Wills underway Identifier: NCT Identifier: NCT patients: STGD and AMD Stem cells survive in subretinal space up to median 22 months No adverse safety events Vision improved in treated eyes Schwartz SD et al, Lancet 2012: 379; Schwartz SD et al, Lancet 2015: 385; Leber s Congenital Amaurosis Early onset, severe vision loss Many Genetic Mutations: AR: RPE65, AIPL1, TULP-1, GUCY2D/RETGC, CRB1, CEP290, LCA5, RDH12, RPGRIP1 Account for 70% of identifiable mutations AD: CRX Genetic Testing: Project

4 LCA: RPE65 Gene Therapy 3 Groups: 2 at U Penn, 1 at UC London, 3 pts each Phase I safety results presented in May 2008 Gene Therapy with RPE65 was well tolerated 1/3 in London and 3/3 at U Penn gained vision Visual acuity Visual field Less nystagmus Ability to move around RPE65 Phase 3 trial update Subretinal AAV2 Sites: University of Iowa: (PI: Stephen Russell) CHOP/Penn (PI: Albert Maguire) Update: Spark, Therapeutics reported results from Pivotal phase 3 clinical trial of SPK-RPE65 10/5/15 SPK-RPE65 Effective Treatment, but not a cure First Randomized, Controlled Phase 3 trial of a gene therapy for a genetic disease Met primary and 2 secondary endpoints Demonstrated restoration of functional vision: change in bilateral mobility testing at 1 year Also showed improvement in light sensitivity Plan to file Biologics License Application with USFDA in 2016 Jacobson et al, NEJM 2015: 372;

5 Retinal Degenerations Update: New treatments for retinal degenerations show potential to improve vision for patients with different stages of vision loss: Prosthetic devices Stem Cell trials: Stargardt, AMD Gene Therapy: Leber s Congenital Amaurosis Emerging Technologies Provide Hope for Patients with Severe Vision Loss! Bainbridge et al, NEJM 2015: 372;