Safety and tolerability of RPESC-RPE transplantation in patients with dry age-related macular degeneration: Low-dose clinical outcomes
Rajesh C. Rao, Brigitte L. Arduini, Susan L. Borden, Dhruv Sareen, Clive N. Svendsen, Paul P. Lee, Charles J. Ryan, Shilpa Kodati, Caroline Nyaiburi, Keith Wolsieffer, Eun Jung Oh, Shuna Park, Glenna Ford, Keith E. Dionne, Sally Temple, Jeffrey H. Stern
Abstract
Retinal pigment epithelium (RPE) cell atrophy in dry age-related macular degeneration (AMD) compromises photoreceptor cell function, leading to vision loss. Stem cell-based RPE replacement therapy aims to reverse disease progression and restore vision. RPESC-RPE-4W, a post-mitotic adult RPE stem cell-derived RPE (RPESC-RPE) progenitor cell product, exhibits consistent safety and efficacy in preclinical studies. The first-in-human clinical trial of RPESC-RPE-4W completed low-dose cohort 1 interventions (NCT04627428). Six subjects received a subretinal suspension of 50,000 RPESC-RPE-4W cells. No significant inflammation, tumor, or product-related serious adverse events were observed. Best-corrected visual acuity in the three worse-seeing group A subjects improved by an average of +21.67 letters from baseline at 12 months. Three better-seeing group B subjects improved by an average of +3.0 letters at 6 months. The positive safety and tolerability outcomes for low-dose cohort 1 enabled dose escalation to mid-dose RPESC-RPE-4W therapy for dry AMD. • Adult RPE stem cells generated RPE progenitor cells at 4 weeks of differentiation • Progenitor-stage RPE cells were implanted to treat dry AMD • Clinical outcomes from low-dose cohort 1 met primary safety endpoints • Visual acuity improvements were greater in worse-seeing subjects Retinal pigment epithelium (RPE) cell loss in dry age-related macular degeneration leads to progressive vision decline. Stern and others implanted adult RPE stem cell-derived RPE progeny at a 4-week progenitor stage of differentiation (RPESC-RPE-4W). First-in-human cohort 1 met primary safety endpoints, with greater visual improvement observed in worse-seeing eyes.