Sophie Cai, MD
Vitreoretinal Surgery Fellow
Duke Eye Center, Durham, NC
Another exciting presentation was given by Dr. Brandon Busbee of Tennessee Retina. Dr. Busbee reported the results of the OPTIC Study, an ongoing multicenter Phase 1 study of an in-office intravitreal injection of ADVM-022 (Adverum Biotechnologies, Redwood City, CA). ADVM-022 is an adeno-associated virus gene therapy for sustained aflibercept protein expression for treatment of neovascular AMD (NVAMD).
Thus far, four cohorts, totaling 30 patients, have been followed for up to 104 weeks, with a 3-year extension study and follow-up Phase 3 trials planned. The cohorts differed in treatment regimen, with two different doses of ADVM-022, and two different steroid prophylaxis regimens (oral versus topical). Supplemental intravitreal aflibercept was permitted in cases of prespecified criteria for worsening of BCVA or CST from baseline or new vision-threatening hemorrhage. Safety and efficacy assessments were performed at 24, 52, and 104 weeks.
The mean baseline VA was 20/50 in all cohorts, and the mean number of intravitreal anti-VEGF injections in the year prior to study enrollment was 7 to 9 in each cohort. Current interim data analysis showed a 96% reduction in the annualized anti-VEGF injection rate in eyes treated with the higher dose of ADVM-022, and 85% reduction in the eyes treated with the lower dose of ADVM-022. BCVA was stable in all groups at last follow-up, with mild decrease in CST compared to baseline in both groups. Aqueous levels of aflibercept expression were maintained over time.
From a safety standpoint, no systemic adverse events were attributed to ADVM-022. No eyes developed endophthalmitis, vasculitis, or posterior uveitis. One eye developed a delayed retinal detachment thought unrelated to ADVM-022. Two eyes developed mild IOP elevation that improved with drops. Anterior chamber and/or vitreous inflammation was the most common ocular event, but was less common with a lower dose of ADVM-022 and also uniformly responsive to topical steroids.
Dr. Busbee concluded that current data are encouraging. A single in-office intravitreal ADVM-022 injection can provide NVAMD patients with a high baseline injection burden the opportunity for sustained visual and anatomic results with minimal supplemental injections for up to 104 weeks and a favorable safety profile. Phase 3 trials are planned later this year.