Multicharacteristic Opsin Gene Therapy Improves BCVA, MLSDT in Retinitis Pigmentosa


High dose MCO-010 yielded statistically significant improvements in BCVA and MLSDT at week 52.

Samuel Barone, MD, chief medical officer, Nanoscope Therapeutics

Samuel Barone, MD

Caption: Nanoscope Therapeutics

Patients with retinitis pigmentosa (RP) treated with high dose MCO-010 gene therapy had statistically significant improvements on best-corrected visual acuity (BCVA) and near-field object recognition from baseline compared with those who received sham injections.

Data from the phase 2b/3 RESTORE trial (NCT04945772) presented at the American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting, held May 7 to 10, 2024, in Baltimore, Maryland, by Samuel Barone, MD, chief medical officer, Nanoscope Therapeutics.

“RP stands as the most prevalent inherited retinal disease globally, impacting over 1.5 million individuals worldwide. With over 90 identified genetic mutations linked to RP, the absence of effective treatments underscores the substantial unmet need,” Barone and colleagues wrote in their poster.

MCO-010 is an optogenetic gene therapy that consists of an adeno-associated virus (AAV2) vector delivering multicharacteristic opsin and is administered via an intravitreal injection. It is designed to transduce bipolar cells to express a photosensitive opsin protein and restore light sensitivity to the retina.

READ MORE: Rod-Cone Dystrophy Gene Therapy Demonstrates Acceptable Safety, Study to Continue

RESTORE randomized 27 participants with RP to receive either 0.9E11 gc/eye MCO-010, 1.2E11 gc/eye MCO-010, or sham injection in the study eye. The participants had baseline BCVA worse than 1.9 LogMAR in the study eye and no better than 1.6 LogMAR in the other eye. BCVA was assessed using Freiburg visual acuity (recommended for individuals with low vision by International HOVER [Harmonization of Outcomes and Vision Endpoints in Vision Restoration Trials] Taskforce).

On BCVA, the low dose cohort had mean improvements of 0.160 (P against sham =.2767), 0.191 (P = .1945), 0.431 (P = 0.0058), and 0.332 LogMAR (P = .0290) at weeks 16, 24, 36, and 52, respectively. The high dose cohort had mean improvements of 0.022 (P against sham = .8403), 0.197 (P = .0772), 0.214 (P = .0549), and 0.287 (P = .0104) at weeks 16, 24, 36, and 52, respectively.

On multi-luminance shape discrimination test (MLSDT), the low dose cohort had mean scores of 0.22 (P from baseline = .8337), 0.00 (P = 1.00), 1.22 (P = .2489), and 1.33 (P = .2721) at weeks 16, 24, 36, and 52, respectively. The high dose cohort had mean scores of 1.11 (P from baseline =.1388), 0.78 (P = .2594), 1.00 (P = .2500), and 1.89 (P = .0265) at weeks 16, 24, 36, and 52, respectively. The sham cohort had mean scores of -0.11 (P from baseline =.8725), 0.33 (P =.6666), -0.11 (P = .5943), and 0.33 (P = .8032) at weeks 16, 24, 36, and 52, respectively.

MCO-010 was well-tolerated and no serious adverse events were reported through week 52.

“RESTORE data demonstrate MCO-010–treated patients improved in BCVA in both dose groups, compared to sham-treated patients, where statistically significant improvements in visual acuity were observed at week 26 and were maintained through the week 52 study. A dose-dependent improvement in near-field object recognition was observed in the MCO-010–treated patients – high dose patients statistically improved in MLSDT at week 52 compared to baseline,” Barone and colleagues concluded. “RESTORE data further support the validity of using Freiburg visual acuity for low-vision patients as an efficacy endpoint. Observations on functional visual assessments support BCVA findings.”

Click here to read more coverage of the 2024 ASGCT Meeting.

Barone S, Chavala SH, Koester J, et al. Longitudinal Analysis of BCVA and Near-Field Object Recognition in Low- or High-Dose MCO-010 Mutation Agnostic Optogenetic Therapy for Retinitis Pigmentosa: 12-Month Results from a Phase 2b/3 Randomized, Sham-Controlled, Patient- and Assessor-Masked Clinical Trial (RESTORE). Presented at: ASGCT 27th Annual Meeting, May 7-10; Baltimore, Maryland. Abstract #917
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