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Gene therapy: emerging strategies in the management of neovascular age-related macular degeneration (nAMD) and other acquired and inherited retinal disorders

Session Details

Session Title: New Drug Treatment and Technology I

Session Date/Time: Friday 18/09/2015 | 11:00-12:30

Paper Time: 11:00

Venue: Thalie.

First Author: : S.Kiss UNITED STATES

Co Author(s): :    J. Mones              

Abstract Details

PURPOSE:In retina practices, the burden of chronic care management is significant. Studies suggest that, compared with clinical trials, real-world patients are monitored less frequently, receive fewer injections, and may have inferior vision results. Moreover, most inherited dystrophies do not currently have any therapy. The purpose is to assess ocular gene therapy as an approach to a variety of retinal disorders.


Department of Ophthalmology, Weill Cornell Medical College; Institut de la Màcula i de la Retina, Barcelona, Spain ; Barcelona Macula Foundation, Barcelona, Spain


For nAMD there are several anti-VEGF gene therapy approaches. Our group constructed an AAV rhesus serotype rh.10 vector to deliver bevacizumab (AAVrh.10BevMab). Genzyme evaluated a novel chimeric anti-VEGF molecule, sFLT01, in an AAV2 vector (AAV2-sFLT01). Avalanche Biotechnologies developed AVA-101, an AAV2 vector with sFLT-1, a naturally occurring anti-VEGF protein with high affinity for VEGF. Other targets currently in development include nAMD (AVA-201) Leber’s congenital amaurosis (LCA, SPK-RPE65) and choroideremia (AAV.REP1), juvenile X-linked Retinoschisis (AAV-311, AGCT), inherited cone disorders (AVA-322, AVA-323), among others.


Preclinical evaluation, by our group, of an injection of AAVrh.10BevMab shows long-term efficacy in a mouse and primate AMD models. In Genzyme’s phase 1 study, intravitreally injected AAV2-sFLT01 was safe and well tolerated. Biological activity was noted in 4 of 11 expected responders. In Avalanche’s phase 1 study, AVA-101 was well-tolerated with no significant vector- or procedure-associated safety concerns. Patients receiving AVA-101 gained or maintained VA with minimal need for rescue treatment at 1 year. For patients requiring numerous anti-VEGF injections prior to enrollment, only 2 of 6 AVA-101 treated subjects required a single rescue injection over 1 year. A phase 3 clinical trial for LCA, SPK-RPE65 from Spark, improved VA and patient quality of life following subretinal administration. Similarly, AAV.REP1, from the University of Oxford, increased retinal sensitivity in the treated eyes of choroideremia patients in phase 1 testing. Avalanche’s AVA-201, AVA-311, AVA-322, and AVA-323 programs are currently in preclinical stages.


Preclinical and clinical data suggest that gene therapy for the long-term treatment of a variety of retinal disorders is practical and well-tolerated. With the initial successes in nAMD and LCA, the spectrum of retinal disorders amiable to gene therapy will undoubtedly continue to expand. The encouraging early results need to be followed up with long-term safety, tolerability and efficacy studies.

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