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Eyal Banin, Yitzchak Hemo, Tareq Jaouni, Devora Marks-Ohana, Maria Gurevich, Oscar Cuzzani, David S Boyer, Benjamin Reubinoff; 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. Invest. Ophthalmol. Vis. Sci. 2018;59(9):77.
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Transplantation studies using autologous RPE cells in AMD patients suggest that introducing healthy RPE cells may be of therapeutic benefit. Over the last decade we developed the technology to derive RPEs from hESC using a directed differentiation, xeno-free GMP protocol. Safety and tolerability of this cell product is 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 first 3 cohorts of patients, who received a subretinal transplant of 50k, 100k or 200k OpRegen cells in suspension, with up to 2 years follow up.
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, color OCT and fundus autofluorescence imaging.
At date of writing, dosing of cohort 3 with 100k cells is ongoing, following completion of the first 2 cohorts of 3 patients each that are now under long term follow-up. Surgeries have been uneventful, with subretinal fluid absorbing within <48 hours. OCT imaging showed healing of the retinal penetration site within 2 weeks following surgery. 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 the majority of 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 to 3 months and persist through the latest time point examined. Of note, epiretinal membranes that did not require surgical intervention were seen in some patients.
Subretinal transplantation of OpRegen hESC-derived RPE cells 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 with improved vision at baseline.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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