Phase I/II open-label study of implantation into one eye of hESC-derived RPE in patients with retinitis pigmentosa due to monogenic mutation: first safety results

Abstract

Purpose : In developed countries, retinal degenerative diseases affecting Retinal Pigmented Epithelium (RPE), including Age-related Macular Dystrophy and inherited retinal diseases such as Retinitis Pigmentosa (RP), are the predominant causes of human blindness worldwide. Despite the scientific advances achieved in the last years, there is no cure for such diseases. In this context, we have developed a cell therapy medicinal product based on our expertise in tissue engineering and in the manipulation of pluripotent stem cells. This novel tissue engineered product (TEP) consists in RPE cells derived from clinical grade human embryonic stem cells disposed on a biocompatible substrate allowing the formation of a 3D functional sheet, suitable for transplantation. After functional validation in a rodent model of RP (Ben M'Barek et al., 2017), we have tested the safety of the surgery and local tolerance in non-human primates (NHP; Ben M’Barek et al., 2020).

Methods : A specific device was developed in order to (i) embed the TEP in gelatin, (ii) allow its transport in a specific medium and (iii) cut the transplant at the right format.

Results : We showed that ERG responses were not modified by the surgery and that it did not cause any long lasting inflammation. Moreover, transplanted cells were integrated in the retina and were able to phagocyte photoreceptor debris. Our surgical method of implantation was safe and did not provoke any local inflammation or retinal deterioration.

Conclusions : These results lay the foundations for the start of a phase I/II clinical trials in 2019 that is now on going (NCT NCT03963154). 7 patients have been transplanted so far and first results are showing no major adverse events with in some of them the stabilization of the nystagmus and fixation.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.