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 : Transplantation studies using autologous RPE cells in AMD patients suggest that introducing healthy RPE cells may be of benefit. Over the last decade we developed the technology to derive RPE cells in-vitro from hESCs using a directed differentiation, xeno-free protocol. Safety and tolerability of this cell product, OpRegen, is now being evaluated in a dose-escalating Phase I/IIa clinical study in patients with advanced dry AMD accompanied by geographic atrophy (NCT02286089). Here we report accumulated safety and imaging data from the 1^st and 2^nd cohorts of patients, who received a subretinal transplant of 50k or 200k OpRegen cells in suspension, with up to 1 year follow up.

Methods : Transplantation was performed by subretinal injection following conventional 23G vitrectomy under local anesthesia. Systemic immunosuppression is administered from 1 week prior to transplantation until 1 year after. Systemic and ocular safety is closely monitored. Retinal function and structure are assessed using various techniques including BCVA, and color, OCT and fundus autofluorescence (FAF) imaging.

Results : At date of writing, dosing of cohort 1 of 3 patients (ages 74-80 years) who received 50k cells has been completed with a follow-up of 1 year, 9 and 6 months, and 2 out of 3 patients from cohort 2 (ages 65 and 82) were dosed with 200k cells. Surgery was uneventful, with subretinal fluid absorbing within <48 hours. OCT imaging showed healing of the retinal penetration site by 2 weeks post-op. Treatment has been well tolerated systemically and with regard to ocular findings. Imaging changes associated with OpRegen include subretinal pigmentation in area of transplant in 4 out of 5 patients, often accompanied by hypo- and hyper-fluorescent spots on FAF imaging and irregular reflectance above areas of atrophy and host RPE on OCT scans. These changes develop over the first 2-3 months and persist through the latest time point examined. Of note, epiretinal membranes that do not require surgical intervention were observed.

Conclusions : Subretinal transplantation of OpRegen in patients with advanced dry AMD appears well tolerated to date. Findings on imaging suggest presence of cells in the subretinal space. These results provide a framework for functional assessments in cohorts at higher doses.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.