Phase I/IIa Clinical Trial of Human Embryonic Stem Cell (hESC)-Derived Retinal Pigmented Epithelium (RPE, OpRegen) Transplantation in Advanced Dry Form Age-Related Macular Degeneration (AMD): Interim Results

Abstract

Purpose : Introduction of healthy RPE cells may be of therapeutic benefit in dry AMD patients. We developed technology to derive RPEs from hESCs using cGMP directed differentiation. Safety and tolerability of these cells is being evaluated in a Phase I/IIa clinical study in patients with dry AMD and geographic atrophy (GA) (NCT02286089). We report accumulated safety and imaging data from all subjects in the fully-enrolled first 3 cohorts (n=12) and ongoing 4^th cohort.

Methods : Subretinal transplantation of 50-200k OpRegen cells in suspension to the worse vision eye uses either pars plana vitrectomy (PPV) and retinotomy or the Orbit subretinal delivery system (SDS) under local anesthesia. Short course, perioperative systemic immunosuppression is used. Systemic and ocular safety is closely observed, and retinal function and structure are monitored using various imaging modalities.

Results : Cohorts 1-3 are in long-term follow-up. Cohort 4 dosing is ongoing. Treatment has been well tolerated to date, with no unexpected adverse events (AEs) or treatment-related systemic serious adverse events reported. Using PPV, the most common ocular AEs were the formation of predominately mild epiretinal membranes (ERM), though two severe ERM were surgically peeled. Additionally, one PPV-treated patient experienced a retinal detachment. All 3 events were successfully treated. AEs associated with the Orbit SDS include eyelid edema and subconjunctival hemorrhage (n=1, each). Visual improvement has been noted in all cohort 4 patients to date (n=4; 10-22 letters), which has been maintained from 4.5 to over 15 months. In several subjects, within the area of RPE cell transplant, improvements of the ellipsoid zone and RPE layers at the border of GA, as well as directional growth changes in the area of GA, have been seen. Persistent changes observed following treatment include, alterations in drusen appearance, subretinal pigmentation and hyper-reflective areas, suggestive of the presence of transplanted RPE cells.

Conclusions : Subretinal transplantation of hESC-derived RPE 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 will require additional follow-up.

This is a 2020 ARVO Annual Meeting abstract.