Nanoscope Therapeutics’ Retinitis Pigmentosa Gene Therapy MCO-010 Improves Visual Acuity in Randomized Controlled Clinical Trial
The randomized, controlled clinical trial treated patients with either a high dose of MCO-010, a low dose of MCO-010, or a sham–control.
Nanoscope Therapeutics’ MCO-010 (sonpiretigene isteparvovec), an investigational ambient-light activatable multi-characteristic opsin (MCO) gene therapy, has improved visual acuity in patients with retinitis pigmentosa (RP) in comparison to patients who received a placebo in data from the phase 2b RESTORE clinical trial (NCT04945772).1 The data were presented at the American Academy of Ophthalmology 2024 Annual Meeting, held October 18 to 21 in Chicago, Illinois.
The randomized, controlled clinical trial treated patients with either a high dose of MCO-010, a low dose of MCO-010, or a sham–control. At 52 weeks posttreatment, patients treated in the high dose cohort showed a mean improvement of 0.337 ± 0.0829 LogMAR in comparison to the sham-control group (P = .0209) and patients treated in the low dose cohort showed a mean improvement of 0.382 ± 0.1244 LogMAR in comparison to the sham-control group (P = .0290). At 76 weeks posttreatment, patients treated in the high dose cohort showed a mean improvement of 0.539 ± 0.1032 LogMAR in comparison to the sham-control group (P = .0014) and patients treated in the low dose cohort showed a mean improvement of 0.374 ± 0.1332 LogMAR in comparison to the sham-control group (P = .0652).
Furthermore, Nanoscope pointed out that at 52 weeks posttreatment 7 of the 18 patients (39%) treated with the gene therapy showed an improvement of at least 0.3 LogMAR in best-corrected visual acuity (BCVA) and at 76 weeks posttreatment 10 of the 18 patients (56%) showed an improvement of at least 0.3 LogMAR. The company also noted that statistically significant mean BCVA improvement in comparison to the sham-control group was seen in longitudinal analysis at visits from 36 to 88 weeks posttreatment. In addition, for both the high dose and low dose groups, the BCVA area under the curve profiles were 5 times greater up to 52, 76, and 100 weeks posttreatment in comparison to the sham-control group.
“The durable statistically significant vision improvement achieved at multiple time points during the 2-year study is highly noteworthy,” Allen C. Ho, MD, FACS, FASRS, the director of retina research and codirector of the Retina Service at Wills Eye Hospital and the chief medical advisor of Nanoscope, who presented the data, said in a statement.1 “This degree of improvement has never been observed in a randomized, controlled trial of a highly heterogeneous severe vision-loss patient population. These findings deliver hope to patients and ophthalmologists that a solution is close to being found. We are finally on the brink of an impactful in-office, mutation-agnostic gene therapy for people with severe vision loss.”
In terms of safety, the gene therapy was characterized as well-tolerated. The most common adverse events among participants in the trial were anterior chamber cell, which occurred in 44% of patients who received MCO-010 and 22% of patients who received the sham-control, and ocular hypertension, which occurred in 39% of patients who received MCO-010 and 22% of patients who received the sham-control. Nanoscope noted that these cases either resolved or were managed with topical medication.
In October 2024, Nanoscope announced that, following a meeting with the FDA that it characterized as “productive”, it intends to pursue a rolling BLA submission for MCO-010 in severe vision loss due to RP, with reference to the fast track designation that the program previously has received from the FDA.2 Nanoscope intends to go forward with the BLA submission in the first quarter of next year.
“We are pleased with the positive interactions we have had with FDA as a result of the exceptional expertise and tireless commitment of the Nanoscope team,” Sulagna Bhattacharya, B. Tech, MBA, the cofounder and CEO of Nanoscope, said in an October 2024 statement.2 “Our shared goal is to change lives, and together, we have advanced MCO-010 to the point of BLA submission. With every step forward, we are focused on the patients who are waiting for meaningful sight restoration. Our team looks forward to continuing the important work we have begun, along with our partners, to bring this therapy to patients who have significant unmet need.”
