Ocugen Inc., (NASDAQ:OCGN), an ophthalmic biopharmaceutical company based in Malvern, Pennsylvania, has announced preliminary safety and efficacy data of a Phase 1/2 study of “OCU400”, a modifier gene therapy candidate for the treatment of retinitis pigmentosa (RP) resulting from mutations in the nuclear receptor subfamily 2 group E member 3 (NR2E3), and Leber Congenital Amaurosis (LCA) with mutation(s) in the CEP290 gene. NR2E3 is a part of a large family of nuclear receptor transcription factors involved in signalling pathways, regulating pathways in embryonic development and in maintenance of proper cell function in adults. The NR2E3 gene encodes a retinal nuclear receptor that is a ligand-dependent transcription factor and defects in this gene are a cause of enhanced S cone syndrome. In addition, Leber Congenital Amaurosis (LCA) with mutation(s) in the CEP290 gene, one of the most frequent genes causing LCA, and also reporting preliminary outcomes for OCU400.
The Phase 1/2 trial is a multi-centre, open-label, dose ranging study with a total of 18 RP subjects enrolled – 10 subjects in the dose escalation and 8 subjects in an expansion phase, respectively. The subjects enrolled ranged from 18-77 years across RHO and NR2E3 gene mutations and a further Phase1/2 trial enrolling LCA patients with CEP290 gene mutation and pediatric patients with NR2E3, RHO and CEP290 mutations. According to the company, 7 participants with severe vision impairment due to RP associated with RHO and NR2E3 gene mutations received a unilateral subretinal injection of either a low dose (1.66 x 1010 vg/mL) or medium dose (3.33 x 1010vg/mL) of OCU400, respectively. Following the preliminary data analysis, 9-month follow-up data reported a favourable safety profile and visual improvements after treatment, as measured by multi-luminance mobility testing (MLMT) and best corrected visual acuity assessment (BCVA). 5 of 7 (71.4%) treated eyes demonstrated a 1 or more Lux level improvement in MLMT score, compared to 28.6 % of untreated eyes; and 66.7% (2 of 3) of treated eyes [in a cohort 1 with 9-month follow-up] demonstrated a 2 or more Lux level improvement in MLMT score, compared to none of the untreated eyes.
Commenting on the announcement, David Birch, PhD, Scientific Director, Retina Foundation of the Southwest, and principal investigator of the study stated that, “I was not expecting such substantial improvements in visual function among the trial participants I have been working with because of the advanced stage of their retinal disease. I am very pleased by the outcomes I have seen in my own clinic and am hopeful that OCU400 could provide a therapeutic solution for RP patients who are not only facing loss of vision, but also challenged with the psychological burden of losing their independence.”