Long-term Follow-up of a Phase 1/2a Clinical Trial of a Stem Cell-Derived Bioengineered Retinal Pigment Epithelium Implant for Geographic Atrophy

Mark S Humayun; Dennis O Clegg; Margot S Dayan; Amir H Kashani; Firas M Rahhal; Robert L Avery; Hani Salehi-Had; Sanford Chen; Clement Chan; Neal Palejwala; April Ingram; Debbie Mitra; Britney O Pennington; Cassidy Hinman; Mohamed A Faynus; Jeffrey K Bailey; Lincoln V Johnson; Jane S Lebkowski

doi:10.1016/j.ophtha.2023.12.028

Long-term Follow-up of a Phase 1/2a Clinical Trial of a Stem Cell-Derived Bioengineered Retinal Pigment Epithelium Implant for Geographic Atrophy

Ophthalmology. 2023 Dec 30:S0161-6420(23)00935-1. doi: 10.1016/j.ophtha.2023.12.028. Online ahead of print.

Authors

Mark S Humayun¹, Dennis O Clegg², Margot S Dayan³, Amir H Kashani⁴, Firas M Rahhal⁵, Robert L Avery⁶, Hani Salehi-Had⁷, Sanford Chen⁸, Clement Chan⁹, Neal Palejwala¹⁰, April Ingram¹¹, Debbie Mitra³, Britney O Pennington¹², Cassidy Hinman¹², Mohamed A Faynus¹², Jeffrey K Bailey¹², Lincoln V Johnson¹¹, Jane S Lebkowski¹¹

Affiliations

¹ USC Roski Eye Institute, USC Ginsburg Institute for Biomedical Therapeutics and Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, California; Department of Biomedical Engineering, University of Southern California, Los Angeles, California. Electronic address: humayun@usc.edu.
² Center for Stem Cell Biology and Engineering, Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, California.
³ USC Roski Eye Institute, USC Ginsburg Institute for Biomedical Therapeutics and Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, California.
⁴ Wilmer Eye Institute, Johns Hopkins School of Medicine, Johns Hopkins University, Baltimore, Maryland.
⁵ Retina-Vitreous Associates Medical Group, Beverly Hills, California.
⁶ California Retina Consultants, Santa Barbara, California.
⁷ Retina Associates of Southern California, Huntington Beach, California.
⁸ Orange County Retina Medical Group, Santa Ana, California.
⁹ Southern California Desert Retina Consultants, Palm Desert, California.
¹⁰ Retinal Consultants of Arizona, Retinal Research Institute LLC, Phoenix, Arizona.
¹¹ Regenerative Patch Technologies, Menlo Park, California.
¹² Center for Stem Cell Biology and Engineering, Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, California; Regenerative Patch Technologies, Menlo Park, California.

PMID: 38160882
DOI: 10.1016/j.ophtha.2023.12.028

Abstract

Purpose: To report long-term results from a phase 1/2a clinical trial assessment of a scaffold-based human embryonic stem cell-derived retinal pigmented epithelium (RPE) implant in patients with advanced geographic atrophy (GA).

Design: A single-arm, open-label phase 1/2a clinical trial approved by the United States Food and Drug Administration.

Participants: Patients were 69-85 years of age at the time of enrollment and were legally blind in the treated eye (best-corrected visual acuity [BCVA], ≤ 20/200) as a result of GA involving the fovea.

Methods: The clinical trial enrolled 16 patients, 15 of whom underwent implantation successfully. The implant was administered to the worse-seeing eye with the use of a custom subretinal insertion device. The companion nonimplanted eye served as the control. The primary endpoint was at 1 year; thereafter, patients were followed up at least yearly.

Main outcome measures: Safety was the primary endpoint of the study. The occurrence and frequency of adverse events (AEs) were determined by scheduled eye examinations, including measurement of BCVA and intraocular pressure and multimodal imaging. Serum antibody titers were collected to monitor systemic humoral immune responses to the implanted cells.

Results: At a median follow-up of 3 years, fundus photography revealed no migration of the implant. No unanticipated, severe, implant-related AEs occurred, and the most common anticipated severe AE (severe retinal hemorrhage) was eliminated in the second cohort (9 patients) through improved intraoperative hemostasis. Nonsevere, transient retinal hemorrhages were noted either during or after surgery in all patients as anticipated for a subretinal surgical procedure. Throughout the median 3-year follow-up, results show that implanted eyes were more likely to improve by > 5 letters of BCVA and were less likely to worsen by > 5 letters compared with nonimplanted eyes.

Conclusions: This report details the long-term follow-up of patients with GA to receive a scaffold-based stem cell-derived bioengineered RPE implant. Results show that the implant, at a median 3-year follow-up, is safe and well tolerated in patients with advanced dry age-related macular degeneration. The safety profile, along with the early indication of efficacy, warrants further clinical evaluation of this novel approach for the treatment of GA.

Financial disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Keywords: Clinical trial; Geographic atrophy; Implant; RPE; Stem cells.