Ocugen Inc., (NASDAQ:OCGN), an ophthalmic biopharmaceutical company based in Malvern, Pennsylvania, has announced positive clinical study update of a Phase 1/2 study of “OCU400”, a modifier gene therapy candidate for the treatment of RP and LCA. The Phase 1/2 trial is aimed to treat RP associated NR2E3 and rhodopsin (RHO) mutations and LCA with mutation(s) in the CEP290 gene. The clinical study update is an extension of previous results on additional subjects and from a high dose cohort. 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 subjects with vision impairment due to RP associated with RHO and NR2E3 gene mutations. Participants received a unilateral subretinal injection of either a low dose (1.66 x 1010 vg/mL), medium dose (3.33 x 1010 vg/mL), or high dose (1.66 x 1011 vg/mL) of OCU400. The study included a group of subjects aged 18-77 years old, with varied disease stages, racial and ethnic profiles, medical histories, and mutation subgroups. Ocugen further expanded the trial to enroll LCA patients with CEP290 gene mutation and pediatric patients with NR2E3, RHO and CEP290 mutations.
According to the update, the company reported key efficacy outcomes from 12 subjects including on BCVA, LLVA and MLMT. On BCVA, 83% (10/12) of subjects demonstrated stabilization or improvements in treated eyes in BCVA scores from baseline. 42% (5/12) of OCU400 treated eyes experienced 4-letter improvement and 33% (4/12) treated eyes experienced 7-letter improvement in BCVA from baseline, and; 57% (4/7) of RHO subjects’ treated eyes experienced 4-letter improvement and 43% (3/7) treated eyes experienced 7-letter improvement in BCVA scores from baseline.
On Low-Luminance Visual Acuity (LLVA), 83% (10/12) of subjects demonstrated stabilization or improvement in treated eyes in LLVA scores from baseline. 42% (5/12) of OCU400 treated eyes experienced 5-letter improvement (1 line) in LLVA from baseline, with 25% (3/7) increasing by 10 letters (2 lines), and 43% (3/7) of RHO subjects experienced 5-letter improvement (1 line) in treated eyes in LLVA scores from baseline, among which 29% (2/7) increased by 10 letters (2 lines)
Finally, on Multi-Luminance Mobility Testing (MLMT), 75% (9/12) of subjects demonstrated stabilization or improvement in treated eyes in MLMT scores from baseline. 33% (4/12) of subjects in the low, medium, and high dose cohorts experienced at least 1 Lux luminance level improvement from baseline in treated eyes, among which 17% (2/12) increased by 3 Lux luminance levels. And, 86% (6/7) of RHO subjects experienced either stabilization or increases in MLMT scores from baseline, among which 29% (2/7) improved by 3 lux levels
Commenting on the summary top-line date, Dr. Shankar Musunuri, Chairman, Chief Executive Officer, and Co-Founder of Ocugen, stated that, “this clinical study update supports our vision to help change the lives of patients suffering from inherited retinal diseases. We remain dedicated to our mission of pioneering breakthroughs in biotechnology and believe that OCU400 has the potential to have an impact on the future treatment of patients with RP and LCA.” In addition, Dr. Lejla Vajzovic, Associate Professor of Ophthalmology, Director of Duke Vitreoretinal Fellowship Program at Duke Eye Center and Duke University School of Medicine commented that, “it is an important steppingstone for Ocugen and its mission to help the nearly 1.6 million patients affected by RP and LCA worldwide. For those suffering from these IRDs, this clinical trial update provides hope. It is encouraging to see a favorable safety and tolerability profile and positive efficacy readout for OCU400 in RP patients.”