Retinal Degenerations Recent Developments Treatments for Patients - - PowerPoint PPT Presentation

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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

Foundation Fighting Blindness USFDA Office of Orphan Product

Development

Lowy Medical Research Institute Research to Prevent Blindness The Claire Giannini Foundation That Man May See, Inc. Lawrence L Hillblom Foundation Neurotech USA, Inc. Foundation Fighting Blindness Spark Therapeutics AGTC Shire California Institute for

Regenerative Medicine

UC Irvine/jCyte Ocugen Okuvision Sucampo AG ISIS Pharmaceuticals

Grant Support Consultant/Scientific Advisory Board

Retinal Degenerations

Diverse group of inherited diseases All associated with progressive loss

• f 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

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Visual Prosthetic Devices

Bypass the missing photoreceptors Stimulate the retinal cells the

photoreceptors talk to: bipolar and ganglion cells

Identify position, orientation, motion of

• bjects

Identify windows, doorways

Retinal Prostheses

Subretinal Prostheses

Second Sight, Model ITM

Epiretinal Prostheses

Retina Implant AGTM

Retina Implant AG Alpha IMS System

3x3 mm2 subretinal microchip 1,500 electrodes, no external camera July 3, 2013: CE Mark approval granted Clinical trial recruiting in Europe

Second Sight Argus II System

Humayun M et al, Ophthalmology 2012: 119; 779-788

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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 415-353-2865, fax 415-514-5870

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

www.ClinicalTrials.gov Identifier: NCT01344993 www.ClinicalTrials.gov Identifier: NCT01345006

Schwartz SD et al, Lancet 2012: 379; 713-20 9 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 2015: 385; 509-16

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 3000

www.carverlab.org

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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

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; 1920-6

Effective Treatment, but not a cure…

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Bainbridge et al, NEJM 2015: 372; 1920-6

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!