Nanoscope Therapeutics' investigational gene therapy, MCO-010 (sonpiretigene isteparvovec), has demonstrated significant and sustained improvements in visual acuity for patients with retinitis pigmentosa (RP) in a Phase 2b clinical trial. The data, presented at the American Academy of Ophthalmology 2024 Annual Meeting, highlight the potential of this ambient-light activatable, multi-characteristic opsin (MCO) gene therapy to address severe vision loss.
RESTORE Trial Results
The randomized, controlled RESTORE trial (NCT04945772) involved patients receiving either a high dose of MCO-010, a low dose of MCO-010, or a sham control. At 52 weeks post-treatment, the high-dose cohort showed a mean improvement of 0.337 ± 0.0829 LogMAR compared to the sham control group (P = .0209). The low-dose cohort also demonstrated a significant mean improvement of 0.382 ± 0.1244 LogMAR compared to the sham control (P = .0290).
Longer-term data at 76 weeks post-treatment revealed even more pronounced benefits. The high-dose cohort exhibited a mean improvement of 0.539 ± 0.1032 LogMAR compared to the sham control group (P = .0014), while the low-dose cohort showed a mean improvement of 0.374 ± 0.1332 LogMAR, although this did not reach statistical significance (P = .0652).
Notably, at 52 weeks, 39% of patients (7 out of 18) treated with the gene therapy experienced an improvement of at least 0.3 LogMAR in best-corrected visual acuity (BCVA). This increased to 56% (10 out of 18) at 76 weeks. Longitudinal analysis from 36 to 88 weeks post-treatment showed statistically significant mean BCVA improvement compared to the sham-control group. Furthermore, the BCVA area under the curve profiles for both high and low-dose groups were five times greater than the sham-control group up to 52, 76, and 100 weeks post-treatment.
Expert Commentary
"The durable statistically significant vision improvement achieved at multiple time points during the 2-year study is highly noteworthy," said Allen C. Ho, MD, FACS, FASRS, director of retina research and co-director of the Retina Service at Wills Eye Hospital, and chief medical advisor of Nanoscope. "This degree of improvement has never been observed in a randomized, controlled trial of a highly heterogeneous severe vision-loss patient population... We are finally on the brink of an impactful in-office, mutation-agnostic gene therapy for people with severe vision loss."
Safety Profile
MCO-010 was generally well-tolerated in the trial. The most common adverse events were anterior chamber cell (44% in the MCO-010 group vs. 22% in the sham-control group) and ocular hypertension (39% in the MCO-010 group vs. 22% in the sham-control group). These cases either resolved or were managed with topical medication.
Regulatory Pathway
Following a productive meeting with the FDA, Nanoscope intends to pursue a rolling BLA submission for MCO-010 in severe vision loss due to RP, leveraging the fast track designation previously granted by the FDA. The company anticipates initiating the BLA submission in the first quarter of 2025.
"We are pleased with the positive interactions we have had with FDA... Our shared goal is to change lives, and together, we have advanced MCO-010 to the point of BLA submission," stated Sulagna Bhattacharya, B. Tech, MBA, cofounder and CEO of Nanoscope. "With every step forward, we are focused on the patients who are waiting for meaningful sight restoration."
