Nanoscope Announces Topline Results from Phase 2b Trial of MCO-010 for Retinitis Pigmentosa
Nanoscope Therapeutics announced positive topline results after the completion of the 2-year phase 2b RESTORE randomized, controlled clinical trial of its lead program, MCO-010, a mutation-agnostic gene therapy for patients with permanent and severe vision loss from advanced retinitis pigmentosa (RP).
The trial met its primary endpoint, demonstrating a statistically significant improvement of best-corrected visual acuity (BCVA) at week 52 in both the high-dose (0.337 LogMAR; P=0.021) and low-dose (0.382 LogMAR; P=0.029) treatment groups compared to the sham control group (0.050 LogMAR). The RESTORE trial represents the only randomized controlled trial in retinal degenerative disease to demonstrate improvement beyond the clinically important BCVA > 0.3 LogMAR threshold in a statistically significant manner, according to Nanoscope.
Improvements in visual function persisted or increased following week 52 in the study, demonstrating the durable effect of a single intravitreal injection of MCO-010. BCVA improvement at week 76, a key secondary endpoint, was statistically significant in the high-dose treatment group compared to the control group (0.539 LogMAR; P=0.001). At week 76, the improvement in BCVA in the low-dose treatment group was not statistically significant compared to control (0.374 LogMAR; P=0.065). These results are consistent with what has been previously observed in the earlier phase 1/2a open-label study. The high-dose MCO-010 (1.2E11gc/eye) is planned to be the commercial dose.
In another prespecified secondary endpoint, the composite functional endpoint of novel multi-luminance shape discrimination and y-mobility testing showed an 89% response rate in both the high-dose and low-dose treatment groups at week 52, offering further support of vision improvement following MCO-010 administration. Additional data from the trial will be presented in a series of scientific meetings in the coming months, beginning with a presentation at the Annual Scientific Meeting of the Association for Research in Vision and Ophthalmology on May 6, 2024, in Seattle, Washington, by Allen Ho, MD, Director of Retina Research and Co-Director of the Retina Service at Wills Eye Hospital.
MCO-010 was generally well tolerated with no treatment-related serious or severe adverse events reported, consistent with prior studies. 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, such as endophthalmitis, retinitis, retinal vasculitis, retinal occlusive vasculitis, or hypotony, were reported in the treatment groups.
“We observed significant vision restoration in many patients with severe vision loss, including those who were completely blind,” David Boyer, MD an investigator in the trial and Adjunct Clinical Professor of Ophthalmology at the University of Southern California Keck School of Medicine, said in a company news release. “Many patients treated with MCO-010 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. If approved, MCO-010 is poised to make a positive, meaningful impact on the lives of patients affected by this debilitating condition.”
Based on these results, Nanoscope intends to submit a BLA to the FDA in the second half of 2024 as the first step in executing its global regulatory and commercialization strategy.
“Nanoscope is at the forefront of advancing optogenetics into a tangible therapeutic solution for patients with RP,” said Sulagna Bhattacharya, co-founder and Chief Executive Officer of Nanoscope. “The compelling data from the most recent analyses of the RESTORE trial at week 76 provide additional validation of Nanoscope’s versatile MCO platform, which is driving our expanding pipeline of programs in both Stargardt disease and geographic atrophy (GA) due to age-related macular degeneration (AMD). We extend our heartfelt appreciation to the trial participants and their families, as well as to the investigators and all those who contributed to this groundbreaking trial and its successful completion.”
These results represent the first evidence of effectiveness of a mutation-agnostic gene therapy for a genetic disease, according to Nanoscope. These results reflect more than a decade of innovation across all aspects of the MCO-010 program, including vector design, manufacturing, and clinical trial design, as well as the development of novel functional vision endpoints for this population with severe vision loss.