Efficacy and safety of MCO-010 optogenetic therapy for vision restoration in patients with severe vision loss due to retinitis pigmentosa: a phase 2b randomized, shamcontrolled, multi-center, multi-dose, doublemasked clinical trial (RESTORE)

Purpose : Retinitis Pigmentosa (RP) is a condition characterized by progressive photoreceptor degradation and eventual profound visual field and vision loss. MCO‐010 is an investigational adeno‐associated virus (AAV2) delivering multi‐characteristic opsins. Optogenetic therapy with MCO‐010 has the potential to restore vision in advanced RP, regardless of causative gene mutation, by photosensitizing bipolar cells thus re‐enabling the retina to sense light. MCO‐010 is activated by ambient light across the visual spectrum, and administered as a single intravitreal (IVT) injection without the need for any external device. RESTORE is a prospective randomized clinical study to assess the efficacy and safety of MCO‐010 in patients with severe vision loss due to RP. Methods : RESTORE is a 2 year, phase 2b, randomized, double‐masked, sham‐controlled multicenter clinical trial evaluating 2 dose levels of intravitreal MCO‐010 in advanced RP (NCT04945772). The primary outcome measure is change from baseline in vision‐guided mobility using the Multi‐Luminance Y‐Mobility Test (MLYMT) at 52 weeks as assessed by central, masked graders. Other key vision function tests include change in visual acuity and performance on the low‐vision multi‐parameter test (LVMPT). Results : 27 patients with clinical signs of advanced RP were enrolled. The 27 subject was randomized in February 2022. 52 week primary efficacy and safety data for all subjects will be presented at the meeting. At screening, mean age was 56 years (range 23‐83). Mean study eye visual acuity was 2.2 LogMAR (range 1.95‐2.25, count fingers/ hand motions vision). As of December 1 2022, 16/27 subjects had completed their week 52 study visit with no serious ocular adverse events or drug‐related systemic adverse events reported. Primary and other key efficacy and safety outcomes data for the entire study will be presented for the first time. Conclusions : MCO‐010 is an optogenetic therapy designed for vision restoration in patients with severe sight loss due to RP. Efficacy and safety data from the RESTORE randomized placebo controlled trial will provide evidence on the benefit/risk profile of MCO‐010 in RP.