RESTORE: MCO-010 Significantly Improves Visual Acuity in Retinitis Pigmentosa

Michael Singer, MD

Credit: Medical Center Ophthalmology Associates

Topline results from the Phase 2b/3 RESTORE trial showed high- and low-dose MCO-010 optogenetic therapy significantly improved best-corrected visual acuity (BCVA) in patients with retinitis pigmentosa. These data were presented at the American Society of Retina Specialists (ASRS) 42nd Annual Meeting.

MCO-010 achieved both the primary and key secondary endpoints in RESTORE, with statistically significant improvement in BCVA for both doses at Week 52 and the high-dose group at Week 76. These clinically meaningful improvements in visual acuity were sustained at Week 100 for ~30% of MCO-010-treated patients.

“In summary, the MCO-010 achieved its primary and secondary endpoint with statistical significance and no serious adverse events,” said presenting investigator Michael Singer, MD, Medical Center Ophthalmology Associates. “There was a clinically meaningful visual improvement in legally blind patients with progressive and permanent neurodegeneration of the retina.”

More than 270 genetic mutations have been linked to inherited retinal diseases (IRDs), the most common of which, retinitis pigmentosa, affects more than 1.5 million people worldwide. No current treatments exist for advanced retinitis pigmentosa, suggesting a large unmet need in IRD care.

MCO-010 is a genetic mutation agnostic optogenetic therapy evaluated in RESTORE for patients with advanced retinitis pigmentosa. MCO-010 delivers a multi-characteristic transgene by intravitreal injection, transducing bipolar cells to express a photosensitive opsin protein and restore light sensitivity to the retina.

These 100-week RESTORE data evaluated the efficacy and safety of a single administration of 2 doses (1.2E11 gc/eye or 0.9E11 gc/eye) of MCO-010 therapy versus sham in patients with retinitis pigmentosa.

Patients had advanced retinitis pigmentosa and a best-corrected visual acuity (BCVA) worse than 1.9 logMAR in the study eye and a fellow eye no better than 1.6 logMAR. Patients received a single intravitreal injection of high-dose MCO-010 (n = 9), low-dose MCO-010 (n = 9), or sham (n = 9), in the study eye at Day 0.

Singer and colleagues assessed BCVA systematically until Week 100 using Freiburg Visual Acuity (VA) test for low-vision patients. In RESTORE, the primary and key secondary endpoints included the mean BCVA change from baseline at Weeks 52 and 76, respectively.

A linear mixed-effects model compared the low- or high-dose MCO-010 cohorts to sham for repeated measures (MMRM), with logMAR score change from baseline as the dependent variable. Treatment group, visit, and group-by-visit interaction were independent variables, and the baseline logMAR score was a covariate.

Upon analysis, at Week 52, patients in the high- and low-dose MCO-010 cohorts experienced statistically significant improvements in BCVA of 0.337 ± 0.0829 (P = .0209) and 0.382 ± 0.1244 logMAR (P = .0290), respectively, versus control. Patients in the control arm exhibited a mean change in BCVA from baseline of 0.050 ± 0.0717 LogMAR

The primary endpoint was met, with 40% of MCO-010-treated patients gaining >0.3 logMAR, equivalent to 3 lines gained.

At Week 76, participants in the high- and low-dose MCO-010 groups experienced mean improvements of 0.539 ± 0.1032 (P = .0014) and 0.374 ± 0.1332 logMAR (P = .0652), respectively, versus control. In the control group, participants had a mean change from baseline of 0.078 ± 0.0737 LogMAR.

The key secondary endpoint was also met, with 56% of MCO-010-treated patients gaining >0.3 logMAR, equivalent to 3 lines gained.

At Week 100, approximately 30% of MCO-010-treated patients achieved clinically meaningful sustained improvements in visual acuity, maintaining the >0.3 logMAR improvement. Safety data at Week 100 revealed no retinitis, choroiditis, vasculitis, ischemic neuropathy, hypopyon, or hypotony in MCO-010-treated patients.

Mild-to-moderate intraocular inflammation (IOI) occurred at the time of steroid tapering, which was met with steroid prophylaxis. Most were treated with topical steroids after initial corticosteroids and by the end of the trial, 17 of 18 patients did not require treatment for IOI at Week 100.

“Vision over the 2-year period shows it’s durable, and the visual function and safety profile are consistent with the Phase 1 trial,” Singer added. “The next stage of MCO-010, for the long-term follow-up, will be presented at future meetings.”

Reference

_{Singer M. Phase 2 Population Extension Cohort in the PRISM Trial Evaluating 4D-150 in Adults With Neovascular Age-related Macular Degeneration. Paper presented at the American Society of Retina Specialists (ASRS) 42nd Annual Meeting. Stockholm, Sweden. July 17-20, 2024.}

_{O'Neal TB, Luther EE. Retinitis Pigmentosa. [Updated 2024 Feb 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK519518/}