June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Anti-VEGF Gene Therapy for Wet AMD: Phase I/II Safety and Pharmacology Results
Author Affiliations & Notes
  • Elizabeth Rakoczy
    Centre for Ophthalmology and Visual Sciences, The University of Western Australia, Perth, WA, Australia
    Molecular Ophthalmology, Lions Eye Institute, Perth, WA, Australia
  • May Lai
    Centre for Ophthalmology and Visual Sciences, The University of Western Australia, Perth, WA, Australia
    Molecular Ophthalmology, Lions Eye Institute, Perth, WA, Australia
  • Cora Pierce
    Molecular Ophthalmology, Lions Eye Institute, Perth, WA, Australia
  • Aaron Magno
    Molecular Ophthalmology, Lions Eye Institute, Perth, WA, Australia
  • Richard Samulski
    Gene Therapy Centre, University of North Carolina, Chapel Hill, NC
  • Thomas Chalberg
    Avalanche Biotechnologies, San Francisco, CA
  • Mark Blumenkranz
    Byers Eye Institute at Stanford, Palo Alto, CA
  • Ian Constable
    Centre for Ophthalmology and Visual Sciences, The University of Western Australia, Perth, WA, Australia
    Molecular Ophthalmology, Lions Eye Institute, Perth, WA, Australia
  • Footnotes
    Commercial Relationships Elizabeth Rakoczy, Avalanche Biotechnologies (C), Lions Eye Institute (P); May Lai, Lions Eye Institute (P); Cora Pierce, None; Aaron Magno, Avalanche Biotechnologies, Inc. (F), Avalanche Biotechnologies, Inc. (R); Richard Samulski, Asklepios BioPharmaceutical, Inc. (I); Thomas Chalberg, Avalanche Biotechnologies, Inc. (E), Avalanche Biotechnologies, Inc. (I), Avalanche Biotechnologies, Inc. (P), Avalanche Biotechnologies, Inc. (S); Mark Blumenkranz, avalanche biotechnologies (I), avalanche biotechnologies (P), optimedica (I); Ian Constable, Lions Eye Institute (P), Avalanche Biotechnologies (C)
  • Footnotes
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Investigative Ophthalmology & Visual Science June 2013, Vol.54, 4091. doi:
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      Elizabeth Rakoczy, May Lai, Cora Pierce, Aaron Magno, Richard Samulski, Thomas Chalberg, Mark Blumenkranz, Ian Constable; Anti-VEGF Gene Therapy for Wet AMD: Phase I/II Safety and Pharmacology Results. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4091.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: To assess the safety and tolerability of rAAV.sFlt-1 following subretinal injection in subjects with exudative age-related macular degeneration (AMD).

Methods: 8 subjects with longstanding and extensively treated exudative AMD were randomized to treatment (6 subjects) or control (2 subjects). All subjects received 0.5 mg ranibizumab at baseline and day 30 to provide anti-VEGF therapy during the initial ramp-up period. Following day 30, ranibizumab was given when a subject met criteria for re-treatment based on visual acuity (VA) and optical coherence tomography (OCT). Seven days after baseline, 6 subjects received rAAV.sFlt-1 (3 low dose: 10E10 vg and 3 high dose: 10E11 vg), administered in 100 ul volume via subretinal injection.

Results: The average age of the patients enrolled for the trial was 79±4.6 years. In all 6 treated subjects, subretinal injection was successfully performed and bleb formation was observed. Serial ophthalmic examinations over time revealed no superficial, anterior segment, or vitreous inflammatory signs in any of the subjects. There was no significant intraocular pressure elevation, retinal detachment, or significant intraocular or systemic inflammation in any patient. Vector sequence was found in the tear of two subjects at one day following rAAV.sFlt-1 injection that cleared by the next sampling time point (14 days post-injection). Vector sequence or AAV capsid were not detected in any other samples. Clinical laboratory assessments, including blood biochemistry, complete blood count, and lymphocyte subsets, remained without any significant change from baseline. Although 50% of subjects had neutralizing antibodies to AAV at baseline, this did not appear to affect safety. Secondary endpoints included apparent visual acuity gains and a 10+ fold reduction in as-needed anti-VEGF injection frequency, with 5/6 treated patients requiring no further injections.

Conclusions: These initial results suggest that subretinal injection of rAAV.sFlt-1 is safe and well-tolerated, and is not associated with systemic or ophthalmic complications even among the elderly.

Keywords: 538 gene transfer/gene therapy • 412 age-related macular degeneration • 453 choroid: neovascularization  
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