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  • Retina/Vitreous

    Ixoberogene soroparvovec (ixo-vec) is a novel intravitreal gene therapy that codes for the aflibercept anti-VEGF protein. According to this early multicenter trial, a single dose of ixo-vec may be able to minimize a patient’s reliance on regular anti-VEGF injections by inducing long-lasting, stable intraocular levels of aflibercept, though larger and longer studies are needed to fully assess the potential of this treatment.

    Study Design

    This was a prospective, open-label, dose-ranging, phase 1 study examining the safety and efficacy of a single dose of intravitreal ixo-vec in patients with wet AMD previously treated with regular intravitreal anti-VEGF injections. Thirty patients enrolled across multiple US study sites were separated into 4 cohorts and treated with low or high doses of ixo-vec (2 × 1011 vs 6 × 1011 vector genomes) and one of 2 prophylactic steroids (oral prednisone or topical difluprednate). Safety was the primary outcome, with efficacy the secondary endpoint (vision, central subfield thickness, and the number of supplemental injections).


    The most common adverse event in both the low- and high-dose groups was anterior chamber cell. All patients in the low-dose group who experienced inflammation were responsive to topical corticosteroids. At the study’s end (week 104), there were no anterior chamber cells or vitreous cells without anti-inflammatory treatment in patients who received the low-dose treatment. No cases of chorioretinal inflammation were reported (i.e., vasculitis, retinitis, or choroiditis). Both groups maintained baseline BCVA and showed stable mean central subfield thickness over 2 years of follow-up. The frequency of anti-VEGF injections decreased in both dosage groups over time, with the mean number of VEGF injections decreasing from approximately 10 injections per year before ixo-vec treatment to 2 injections per year and 0.2 injections per year in the low-dose and high-dose ixo-vec groups, respectively. At the end of the study, 53% (8/15) of participants in the low-dose group and 80% (12/15) of participants in the high-dose group were free of supplemental injections.


    This was a small study with no control or comparator arm and variable patient baseline characteristics. The inflammation adverse events may also be more impactful in a larger cohort.

    Clinical Significance

    This is a successful proof-of-concept study demonstrating the use of intravitreal gene therapy for diseases currently being managed with anti-VEGF injections. However, there are still significant safety concerns surrounding inflammation, especially at higher ixo-vec doses, and a need for larger, controlled studies to further evaluate therapeutic potential.

    Financial Disclosures: Dr. Ajay Kuriyan discloses financial relationships with 4DMT, Adverum, Annexon, National Eye Institute, Novartis, Alcon Pharmaceuticals (Grant Support); Alimera Sciences, Allergan, Bausch + Lomb, EyePoint Pharmaceuticals (Consultant/Advisor); Iveric Bio, Optos (Lecture Fees/Speakers Bureau); Lumata Health, Recens Medical (Consultant/Advisor, Private Equity/Stock Holder); Spark Therapeutics (Consultant/Advisor, Lecture Fees/Speakers Bureau); Genentech (Consultant/Advisor, Lecture Fees/Speakers Bureau, Grant Support).