Phase I/IIa Clinical Trial of Transplanted Allogeneic Retinal Pigmented Epithelium (RPE, OpRegen) Cells in Advanced Dry Age-Related Macular Degeneration (AMD): Interim Results

Abstract

Purpose : Transplanted healthy RPE cells may benefit AMD patients. We created allogenic RPE cells (OpRegen) using directed differentiation. Safety and tolerability of OpRegen is being evaluated in a Phase I/IIa clinical study in patients with dry AMD and geographic atrophy (GA) (NCT02286089). We report interim safety and imaging data from all patients in the fully enrolled study (N=24).

Methods : Subretinal transplantation of 50-200k OpRegen cells in suspension to the worse vision eye used either pars plana vitrectomy (PPV) and retinotomy or the Orbit^TM Subretinal Delivery System (SDS). Short course, perioperative systemic immunosuppression was used. Endpoints include systemic/ocular safety and retinal structure/function.

Results : Patients (VA <20/200) in cohorts 1-3 are in long-term follow-up (10/12; 2-5 years) or withdrawn (2/12). 12 better seeing patients (<20/64) in cohort 4 completed dosing in November 2020 (7 PPV:5 SDS). OpRegen has been well tolerated to date, with no unexpected adverse events (AEs). Using PPV, the most common ocular AEs were epiretinal membranes (ERM), in 15/17 (88%) eyes, mostly mild to moderate; 3 (18%) severe ERM required surgical peeling. 2 PPV-treated patients (2/17;12%) developed retinal detachments, which were successfully treated. AEs, all mild, in Orbit SDS patients included one asymptomatic extramacular type 2 CNV, successfully treated with a single anti-VEGF injection, and subretinal hemorrhage (3/7;43%), all self-resolved without sequelae. Subretinal delivery of OpRegen was successful in 7/7 patients by 5 different surgeons. Improvement or maintenance of baseline visual acuity has been noted in 11/12 (92%) cohort 4 patients (-9 to +19 letters), which has been maintained from 2 months to >2 years. Treatment effects, including alterations in drusen appearance, subretinal pigmentation and hyper-reflective areas, suggest persistence of transplanted OpRegen. One patient has potential signs of retinal restoration and reduction in GA area based on OCT analyses of the periphery of the GA, which continues to be followed.

Conclusions : Subretinal transplantation of OpRegen cells in patients with dry AMD and GA appears well tolerated. Imaging findings suggest presence of transplanted cells in the subretinal space. Encouraging structural and clinical changes observed in some patients are being followed.

This is a 2021 ARVO Annual Meeting abstract.