Phase 1 Study of Intravitreal Gene Therapy with ADVM-022 for neovascular AMD (OPTIC Trial)

Abstract

Purpose : 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.

Methods : 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.

Results : 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.

Conclusions : 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.