Three-year data from the REMAIN extension of the RESTORE phase 2b/3 randomized controlled trial presented at the 2026 ARVO meeting described the durability of MCO-010 (Nanoscope Therapeutics), a disease-agnostic optogenetic gene therapy for advanced retinitis pigmentosa (RP). MCO-010 employs an intravitreal AAV2 vector to induce multicharacteristic opsin (MCO) expression in bipolar cells. MCO conveys light sensitivity to bipolar cells, bypassing degenerated photoreceptors, and restoring the potential for vision. REMAIN is the long-term follow-up study of the Phase 2b/3 RESTORE trial.
In RESTORE, 27 patients with advanced RP (best-corrected visual acuity [BCVA] no better than 20/1600 in the study eye) were randomized to high-dose (1.2×10¹¹ gc/eye; n=9), low-dose (0.9×10¹¹ gc/eye; n=9), or sham (n=9). The primary endpoint was BCVA change from baseline at week 52. At 52 weeks, both treatment arms demonstrated statistically significant best-corrected visual acuity (BCVA) improvements vs sham: mean BCVA change from baseline was 0.337±0.083 (vs sham, P=.021) for the high-dose group, and 0.382±0.124 (vs sham P=.029) for the low-dose group.
Long-term follow-up through 152 weeks in REMAIN showed sustained gains, with mean BCVA improvements of +0.265±0.112 LogMAR (high dose) and +0.456± 0.140 LogMAR (low dose), approximating a ~3-line ETDRS benefit. Greater efficacy was associated with better baseline visual acuity, and less retinal thinning (baseline central subfield thickness >150 µm on OCT). Genetic mutation did not impact outcome.
No treatment-related serious adverse events were reported over 3 years, supporting a favorable safety profile. These findings suggest durable, clinically meaningful visual improvement following a single intravitreal administration, with anatomic and disease-stage variables influencing response.
“The science behind the protein engineering truly differentiates MCO-010, with randomized clinical trial results demonstrating a level of durable vision gain not seen before in this low-vision patient population,” said lead author Vinit B. Mahajan, MD, PhD, a professor, vitreoretinal surgeon, and research scientist in the Department of Ophthalmology at Stanford University. “Optogenetics has the potential to revolutionize the treatment of patients with retinal degeneration.”