MCO-010 Phase 2b Data Supports BLA Submission for Retinitis Pigmentosa


Nanoscope Therapeutics received feedback from the FDA endorsing significant change in BCVA as a primary endpoint supporting approval.

Arshad M. Khanani, MD, MA, FASRS, Director of Clinical Research, Sierra Eye Associates and Clinical Professor, Reno School of Medicine, University of Nevada

Arshad M. Khanani, MD, MA, FASRS

The Phase 2b RESTORE trial (NCT04945772) evaluating MCO-010 (sonpiretigene isteparvovec; Nanoscope Therapeutics) in patients with retinitis pigmentosa (RP) met its primary and secondary endpoints, significantly improving best-corrected visual acuity (BCVA) with no serious adverse events (AEs).1

“We observed significant vision restoration in many patients with severe vision loss, including those who were completely blind,” investigator David Boyer, MD, Adjunct Clinical Professor of Ophthalmology, Keck School of Medicine, University of Southern California, said in a statement.1 “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.”

Nanoscope plans to submit a Biologics License Application (BLA) to FDA in the second half of 2024. The company previously received positive feedback from the FDA that change from baseline in a measure of visual acuity in low vision patients could be an appropriate primary efficacy assessment in an adequate and well-controlled study to support a BLA approval.2 Nanoscope announced the feedback in January along with positive feedback from the Icelandic Medicines Agency similarly endorsing the endpoint.

"Consistent input from both the FDA and IMA on the potential for visual acuity to serve as the primary endpoint for the clinical program is a major milestone for Nanoscope and provides MCO-010 with a clear regulatory path in the US and in Europe," Sulagna Bhattacharya, Co-founder, and CEO of Nanoscope, said in a statement at that time.2

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The RESTORE trial included 28 participants with severe vision loss and a clinically confirmed diagnosis of RP, 18 of which were randomized to receive MCO-010 and 9 of which were randomized to the control group. One participant withdrew from the study before any intervention.

Patients treated with MCO-010 demonstrated a statistically significant improvement of BCVA at week 52 at both the high-dose (0.337 LogMAR; P = .021) and low-dose (0.382 LogMAR; P = .029) levels compared to the sham control group (0.050 LogMAR). Nanoscope noted that a statistically significant improvement in BCVA over 0.3 LogMAR threshold is considered clinically important.1

MCO-010's effect was found to be durable past week 52, with statistically significant improvements at week 76 in the high-dose group compared with the control group, a key secondary endpoint (0.539 LogMAR; P = .001). There was a non-statistically significant trend of improvement compared with control in the low dose group (0.374 LogMAR; P = .065).1

Participants in both the high and low dose groups also showed an 89% response rate in a secondary endpoint, the composite functional endpoint of novel multi-luminance shape discrimination and y-mobility testing at week 52. Further data from RESTORE will be presented at the Annual Scientific Meeting of the Association for Research in Vision and Ophthalmology (ARVO) 2024 meeting.1

MCO-010 was generally well tolerated with no serious AEs reported. Common AEs included mild-to-moderate anterior chamber cell and ocular hypertension. There were no AEs of special interest reported that were related to intraocular inflammation (endophthalmitis, retinitis, retinal vasculitis, retinal occlusive vasculitis, or hypotony).

MCO-010 is an ambient-light activatable multicharacteristic opsin optogenetic monotherapy, delivered via intravitreal injection, that targets inner retinal neurons. Nanoscope Therapeutics is also evaluating the therapy in patients with Stargardt disease.

“I am thrilled to see that MCO-010 has the potential to improve vision in patients with advanced RP,” investigator Arshad M. Khanani, MD, MA, FASRS, Director of Clinical Research, Sierra Eye Associates and Clinical Professor, Reno School of Medicine, University of Nevada, added.1 “This is a pivotal moment for the field of ocular gene therapy to have a potential intravitreal mutation-agnostic treatment for RP, a disease that has no available treatment currently and leads to permanent vision loss.”

1. Nanoscope Therapeutics Announces Positive Top-line Results from Randomized Controlled Trial of MCO-010 for Retinitis Pigmentosa. News release. Nanoscope Therapeutics. March 26, 2024.
2. Nanoscope Therapeutics Provides Regulatory Update on MCO-010 for the Treatment of Retinitis Pigmentosa. News release. Nanoscope Therapeutics. January 18, 2024.
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