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Brandon Busbee, David S Boyer, Arshad M. Khanani, Charles Clifton Wykoff, Dante Joseph Pieramici, Carl Regillo, Carl J Danzig, Brian C Joondeph, James Major, Carol Hoang, Adam Turpcu, Carol Chung, Szilard Kiss, Mehdi Gasmi, Aaron Osborne; Phase 1 Study of Intravitreal Gene Therapy with ADVM-022 for neovascular AMD (OPTIC Trial). Invest. Ophthalmol. Vis. Sci. 2021;62(8):352.
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Intravitreal gene therapy has the potential to significantly reduce treatment burden and improve vision outcomes in patients with neovascular AMD (nAMD). OPTIC is a phase 1 study designed to assess the safety, tolerability and efficacy of a single intravitreal injection of ADVM-022 (AAV.7m8-aflibercept gene therapy) in patients with nAMD.
Open-label, multicenter, dose-ranging study in treatment-experienced patients with a previous confirmed response to anti-VEGF therapy. Patients were administered a single intravitreal injection of ADVM-022 at 6x10^11 vg/eye (Cohort 1: n=6, Cohort 4: n=9) or at 2x10^11 vg/eye (Cohort 2: n=6, Cohort 3: n=9). Incidence and severity of adverse events, change in visual acuity (BCVA), change in central retinal thickness (CST), need for and number of supplemental aflibercept injections were evaluated.
As of October 15, 2020, median follow-up was 86 weeks (Cohort 1), 64 weeks (Cohort 2), 48 weeks (Cohort 3) and 16 weeks (Cohort 4). Patients in all 4 cohorts previously received frequent anti-VEGF injections (mean 7.1–9.2 injections in the prior 12 months) to maintain relatively good baseline BCVA (mean 65.0–65.9 ETDRS letters) prior to receiving ADVM-022. ADVM-022 continues to be well tolerated with a favorable safety profile. All ADVM-022-related ocular adverse events were mild (78%) to moderate (22%). Ocular inflammation predominantly affecting the anterior segment, when observed, has been responsive to steroid eye drops. No cases of retinal involvement or vasculitis were reported. A significant reduction in anti-VEGF injection burden was observed with both doses; 14/15 patients receiving high dose and 10/15 patients receiving low dose remained supplemental anti-VEGF injection free while mean annualized anti-VEGF injection frequency was reduced by 99% (high dose) and 85% (low dose) after ADVM-022. For Cohorts 1–3, data pending for cohort 4, BCVA was maintained with a mean change of -2.5 to +0.2 ETDRS letters, and CST improved with a mean change of -19.7 to -132.7 µm.
ADVM-022 is designed to provide continuous expression of aflibercept following a single intravitreal injection. Over 80% of patients with nAMD treated with a single injection of ADVM-022 in OPTIC have not needed any supplemental anti-VEGF injections up to 92 weeks follow-up. ADVM-022 has the potential to reduce treatment burden and improve patient vision outcomes.
This is a 2021 ARVO Annual Meeting abstract.
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