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 : Studies using autologous RPE cells in AMD patients suggest that introducing healthy RPE cells may be of therapeutic benefit. We developed technology to derive RPEs from hESCs using GMP directed differentiation. Safety and tolerability of this cell product is being evaluated in a Phase I/IIa clinical study in patients with advanced 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 : Transplantation is performed by subretinal injection of 50-200k OpRegen cells in suspension to the worse vision eye following conventional 23G vitrectomy under local anesthesia. Systemic immunosuppression is administered prior to transplantation until 3 months after implantation. Systemic and ocular safety is closely monitored. Retinal function and structure are monitored using various imaging modalities including BCVA, color fundus, SD-OCT, and FAF.

Results : Following completion of the first 3 cohorts, now under long term follow-up, dosing of cohort 4 is ongoing. Overall, treatment has been well tolerated and there have been no unexpected adverse events (AEs) or treatment-related systemic serious adverse events reported. The most common ocular AEs were the formation of predominately mild epiretinal membranes (ERM), though one severe ERM was successfully peeled 2 months following dosing. Additionally, one patient experienced a retinal detachment. Causality of the event was not able to be determined and the patient continues in the study following successful surgical repair. Within the area of the RPE cell transplant, signs of changes in drusen as well as improvements of the ellipsoid zone and RPE layers at the border of GA were seen in some subjects. Persistent changes observed following treatment, including subretinal pigmentation and hyper-reflective areas on OCT, are suggestive of the continued presence of transplanted RPE cells.

Conclusions : Subretinal transplantation of hESC-derived RPE cells in patients with advanced dry AMD and GA appears well tolerated to date. Imaging findings suggest presence of transplanted cells in the subretinal space. Potentially positive structural and clinical changes observed in some patients will require additional follow-up over time.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.