Safety and Efficacy of a Phase 1/2a Clinical Trial of Transplanted Allogeneic Retinal Pigmented Epithelium (RPE, OpRegen) Cells in Advanced Dry Age-Related Macular Degeneration (AMD)

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 1/2a clinical study in patients with dry AMD and geographic atrophy (GA) (NCT02286089). We report safety and imaging data from the primary endpoint for all patients (N=24).

Methods : Subretinal transplantation of 50-200k OpRegen cells in suspension were delivered to the worse vision eye via pars plana vitrectomy (PPV) and retinotomy (n=17) or via a suprachoroidal route (n=7). Short course, perioperative systemic immunosuppression was used. Endpoints include systemic/ocular safety and retinal structure/function.

Results : Patients in cohorts 1-3 (<20/200) have completed (4/12), entered long-term follow-up (F/U) (6/12; 3-5 yrs) or withdrawn (2/12). Cohort 4 patients (<20/64) continue in F/U (11/12; 1-3 yrs, 1 withdrawal). OpRegen has been well tolerated to date, with no unexpected adverse events (AEs). Using PPV, the most common ocular AEs were mild to moderate epiretinal membranes (ERM) (15/17; 88%); 3 (18%) severe ERM required surgical peeling. Two PPV-treated patients (2/17; 12%) developed retinal detachments, which were successfully treated. In patients treated via a suprachoroidal route, 3 mild AEs of CNV were reported; one successfully treated with a single anti-VEGF injection; 2 responsive to regular administration. Disease in cohorts 1-3 typically progressed as expected in advanced GA. However, in cohort 4 patients, improvement or maintenance of baseline visual acuity has been noted in 9/12 (75%) (-2 to +24 letters). Treatment effects, including alterations in drusen appearance, subretinal pigmentation and hyper-reflective areas, suggest persistence of transplanted OpRegen. Patients with atrophic areas extensively covered by the subretinal surgical bleb containing the cell suspension (4/12) have potential signs of outer retinal restoration and reduction in GA area based on OCT analyses of the periphery of the GA compared to baseline imaging.

Conclusions : Subretinal transplantation of OpRegen cells in dry AMD and GA patients 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 abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.