Abstract
Purpose :
MCO-010 is an agnostic optogenetic therapy that has completed Phase 2a clinical trials in patients with Stargardt disease. MCO-010 is an AAV2-delivered multi-characteristic opsin (MCO) administered by intravitreal injection. MCO-010 transduces bipolar cells to express a photosensitive opsin protein, giving the potential to restore light sensitivity to the retina. Here, we performed a longitudinal analysis of visual acuity over the course of 48 weeks in Stargardt patients with macular degeneration treated with a single dose of MCO-010 from the Phase 2a STARLIGHT trial.
Methods :
Enrolled subjects had a clinical diagnosis of Stargardt disease and pathogenic genetic mutations in ABCA4,where 3 patients presented with macular degeneration upon enrollment. Subjects (n = 6) received a single intravitreal injection of 1.2E11 gc/eye MCO-010 in the worse eye at baseline. Endpoints were safety and efficacy, where efficacy was assessed systematically through 48 weeks by best-corrected visual acuity (BCVA) using ETDRS letters, with and without a wearable magnifier. Data were analyzed comparing the ETDRS letter scores obtained throughout the study to baseline.
Results :
Of the patients with a macular degeneration phenotype, at baseline the mean BCVA ETDRS letter score was 18 (range 9-32) in the study eye. At 12, 24, and 48 weeks, the mean improvement in BCVA was 14 (range 3-29), 14 (range 3-29), and 12 letters (range 2-27), respectively. With a wearable magnifier the mean letter score was 31 letters (range 22-27) at baseline. At 12, 24, and 48 weeks, the mean improvement in BCVA was 28 (range 20-33), 30 (range 22-35), and 31 letters (range 30-32), respectively. MCO-010 treatment was well tolerated in these patients. There were no intraocular inflammation events greater than a grade of 2+ and no serious adverse effects.
Conclusions :
Stargardt patients with predominantly macular disease experienced clinically meaningful improvements in BCVA that were maintained through the 48-week study. STARLIGHT is the first clinical study of optogenetic therapy for Stargardt disease. MCO-010 is a promising approach, and outcomes from STARLIGHT will help inform the future clinical development of MCO-010 therapy for vision restoration in Stargardt disease and other retinal degenerative conditions.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.