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

Authors:
Banin, Eyal1, Reimann, Christopher2, Barak, Adiel3; Boyer, David4; Ehrlich, Rita5; Jaouni, Tareq2; McDonald, Richard6; Telander, David G.7; Keane, Michael8; Ackert, Jessica8; Ferguson, Mark D.8; Shabat, Avi Ben-9; Monés, Jordi M.10; Velez, Joyce11; Hogge, Gary S.11; Reubinoff, Benjamin12

Institutions:

1. Center for Retinal and Macular Degenerations, Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. 2. Cincinnati Eye Institute & University of Cincinnati School of Medicine, Cincinnati, Ohio, USA. 3. Sourasky Medical Center, Tel Aviv, Israel. 4. Retina Vitreous Associates Medical Group, Los Angeles, CA, USA. 5. Rabin Medical Center, Petah Tikva, Israel. 6. West Coast Retina Group, San Francisco, CA, USA. 7. Retinal Consultants Medical Group, Sacramento, CA, USA. 8. Gyroscope Therapeutics, Ambler, PA, USA. 9. Lineage Cell Therapeutics, Inc. (Cell Cure Neurosciences, Ltd.,) Jerusalem, Israel. 10. Institut de la Màcula, Barcelona, Spain. 11. Lineage Cell Therapeutics, Inc., Carlsbad, CA, USA. 12. Center for Embryonic Stem Cells Goldyn Savad Institute of Gene Therapy and the Department of Gynecology and Obstetrics, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Transplantation of RPE cells may be of therapeutic benefit in AMD. We developed RPE cells 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 17 subjects.
RPE cells in suspension (OpRegen; 50-200k) were subretinally transplanted under local anesthesia to the worse vision eye using either pars plana vitrectomy (PPV) and retinotomy or via an alternative surgical approach utilizing Gyroscope`s Orbit Subretinal Delivery System. RPE cells ready for onsite thawing and immediate transplantation have also been evaluated. Short course perioperatively systemic immunosuppression is used. Systemic and ocular safety is closely observed, and retinal function and structure are monitored using various imaging modalities.
Treatment has been well tolerated and there have been no unexpected adverse events (AEs) or treatment-related systemic serious AEs. Visual improvement has been noted in all patients of cohort 4. 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, has 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. In conclusion, 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.