RESTORE: MCO-010 Achieves Significant Vision Restoration in Retinitis Pigmentosa

Positive, topline results from the two-year phase 2b RESTORE randomized, controlled trial showed MCO-010 achieved both primary and key secondary endpoints with statistical significance in patients with permanent and severe vision loss from advanced retinitis pigmentosa (RP).

Results from RESTORE, the first randomized, controlled trial of mutation-agnostic gene therapy for a genetic disease, demonstrated clinically meaningful improvement in best-corrected visual acuity (BCVA) with MCO-010 in legally blind individuals with neurodegeneration of the retina.

Based on these positive results, Nanoscope Therapeutics has announced its intention to submit a Biologics License Application (BLA) to the US Food and Drug Administration (FDA) in the second half of 2024, as the first step in its global regulatory and commercialization strategy.

“I am thrilled to see that MCO-010 has the potential to improve vision in patients with advanced retinitis pigmentosa,” Arshad M. Khanani, MD, MA, director of clinical research at Sierra Eye Associates and clinical professor at the University of Nevada, Reno School of Medicine, said in a statement. “This is a pivotal moment for the field of ocular gene therapy to have a potential intravitreal mutation-agnostic treatment for retinitis pigmentosa, a disease that has no available treatment currently and leads to permanent vision loss.”

RESTORE randomized 28 individuals with severe vision loss and a confirmed clinical diagnosis of RP. Participants were evaluated at multiple time points over two years to assess BCVA, measured by the Freiburg visual acuity test. These reported results were from the modified intention-to-treat population including all randomized subjects who received MCO-010 (n = 18) or control (n = 9) in the study eye.

Primary and key secondary endpoints aligned with regulatory discussions with the FDA in January 2024 and aligned the study endpoints with the originally intended study objectives. A revised statistical analysis plan was complemented and submitted to regulatory before week 76 and later time points.

Upon analysis, the trial met its primary endpoint, with statistically significant improvement of BCVA at week 52 in both the high-dose (0.337 logMAR; P = .021) and low-dose (0.382 logMAR; P = .029) MCO-010 treatment groups, compared with sham control (0.050 logMAR).

Nanoscope indicated the RESTORE trial represented the only randomized controlled trial in retina degenerative diseases to show improvement beyond the clinically important BCVA >0.3 logMAR threshold in a statistically significant manner.

Improvements in visual function continued or increased after week 52 of the study, suggesting the durability of a single intravitreal injection of MCO-010. The improvement in BCVA at week 76, a key secondary endpoint, was statistically significant in the high-dose treatment group compared with control (0.539 logMAR; P = .001). In contrast, the improvement in BCVA in the low-dose treatment group was not statistically significant, compared with control, at week 76 (0.374 logMAR; P = .065).

Another pre-specified secondary endpoint revealed the composite functional endpoint of novel multi-luminance shape discrimination and y-mobility testing exhibited an 89% response rate in both the high-dose and low-dose treatment groups at week 52, supporting vision improvement after MCO-010 treatment.

Safety reports showed MCO-010 was mostly well-tolerated, without reports of treatment-related serious or severe adverse events. The most common adverse events were mild or moderate anterior chamber cell and ocular hypertension—no adverse events of special interest related to intraocular inflammation, including endophthalmitis, retinitis, or retinal vasculitis, were reported in the MCO-010 treatment groups.

Overall, results from RESTORE were indicated to have remained consistent with previous observations from the Phase 1/2a open-label study. Nanoscope announced its plan for the high-dose MCO-010 to be the commercial dose, pending FDA approval.

“Many patients treated with MCO-10 derived a clinically meaningful benefit measurable on the primary visual function test, and this effect was confirmed by a parallel improvement in functional vision assessments,” David Boyer, MD, adjunct clinical professor of ophthalmology at the University of Southern California Keck School of Medicine, said in a statement. “If approved, MCO-010 is poised to make a positive, meaningful impact on the lives of patients affected by this debilitating condition.”

References

1. _{Therapeutics N. Nanoscope therapeutics announces positive top-line results from randomized controlled trial of MCO-010 for retinitis pigmentosa. Nanoscope Therapeutics Announces Positive Top-line Results from Randomized Controlled Trial of MCO-010 for Retinitis Pigmentosa. March 26, 2024. Accessed April 2, 2024. https://www.prnewswire.com/news-releases/nanoscope-therapeutics-announces-positive-top-line-results-from-randomized-controlled-trial-of-mco-010-for-retinitis-pigmentosa-302098510.html.}
2. _{Iapoce C. MCO-010 gene therapy for retinitis pigmentosa receives regulatory feedback. HCP Live. January 18, 2024. Accessed April 2, 2024. https://www.hcplive.com/view/mco-010-gene-therapy-retinitis-pigmentosa-receives-regulatory-feedback.}