Abstract
Purpose :
MCO-010 is a gene mutation agnostic optogenetic therapy being evaluated in an ongoing Phase 2b/3 RESTORE clinical trial in individuals with advanced retinitis pigmentosa (RP). We performed an analysis of 52-week longitudinal data to evaluate the efficacy of a single administration of 2 different doses of MCO-010 therapy vs sham. MCO-010 is an AAV2-delivered multi-characteristic opsin (MCO) transgene administered by intravitreal injection. MCO-010 transduces bipolar cells to express a photosensitive opsin protein, restoring light sensitivity to the retina in patients with permanent photoreceptor loss.
Methods :
Subjects had an advanced RP clinical diagnosis and a baseline visual acuity worse than 1.9 logMAR in the study eye and no better than 1.6 logMAR in the fellow eye. Subjects received a single dose of 0.9E11 gc/eye (low-dose; n = 9) or 1.2E11 gc/eye (high-dose; n = 9) MCO-010, or sham (n = 9), in the study eye at day 0. Visual acuity was assessed systematically until week 52 by best-corrected visual acuity (BCVA) using Freiburg visual acuity. Data were analyzed comparing the low- or high-dose MCO-010–treated individuals vs sham using a mixed-effects model for repeated measures with treatment, visit, and treatment-by-visit interaction as factors in the model, using the baseline score as a covariate.
Results :
MCO-010 patients had mean baseline BCVA scores of 2.207 ± 0.105 and 2.250 ± 0.00 logMAR (low- and high-dose, respectively), and the sham patients had a mean baseline BCVA of 2.172 ± 0.1342 logMAR. The following BCVA results are reported from weeks 16, 24, 36, and 52. Compared to sham, low-dose MCO-010 patients had a mean improvement of 0.171, 0.207, 0.438, and 0.337 logMAR (P = 0.2242, 0.1424, 0.0021, and 0.0164, respectively). High-dose MCO-010 patients had a mean improvement of 0.077, 0.220, 0.228, and 0.301 logMAR (vs sham; P = 0.6016, 0.1277, 0.1091, and 0.0355, respectively). MCO-010 was well tolerated with no serious adverse effects observed through week 52.
Conclusions :
RESTORE data demonstrate MCO-010–treated patients improved in BCVA compared to sham-treated patients in both dose groups, where statistically significant improvements in visual acuity was reported at week 36 and was maintained through the 52-week study.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.