Ocugen Announces Positive Update from the Phase 1/2 Trial of OCU400, a Gene Therapy Candidate for the Treatment of RP and LCA

Ocugen announced a clinical study update for retinitis pigmentosa (RP) participants treated in the phase 1/2 trial to assess the safety and efficacy of OCU400 for RP associated with NR2E3 and Rhodopsin (RHO) mutations, and Leber congenital amaurosis (LCA) with mutation(s) in the CEP290 gene. This clinical study update is an extension of results provided by Ocugen on April 14, 2023, and includes additional subjects from the high dose group. The company stated it believes that OCU400—Ocugen’s therapeutic approach utilizing a proprietary modifier gene therapy platform—has the potential to be a gene-agnostic therapeutic for RP and LCA patients with inherited retinal degeneration.

The phase 1/2 trial is a multicenter, open-label, dose ranging study in which 18 subjects with 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), medium dose (3.33 x 1010 vg/mL), or high dose (1.66 x 1011 vg/mL) of OCU400. The study profile included a diverse group of subjects aged 18-77 years old, with varied disease stages, racial and ethnic profiles, medical histories, and mutation subgroups. Ocugen further expanded this phase1/2 trial to enroll LCA patients with CEP290 gene mutation and pediatric patients with NR2E3, RHO, and CEP290 mutations.

The clinical study update is based on the currently available data from phase 1 (dose-escalation: Cohort 1, 2 and 3) and the phase 2 (open enrollment) portion of the study. The exploratory efficacy update includes data for 12 subjects who have completed a minimum of 6-month follow up. The data set comprised of 2 subjects [Cohort 1] with 12-month follow-up; 5 subjects [N=2 from Cohort 1 and N=3 from Cohort 2] with 9-month follow-up; and 5 subjects [N=2 from Cohort 3 and N=3 from Open Enrollment/Phase 2] with 6-month follow-up.

Key efficacy outcomes from 12 subjects demonstrated:

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
• 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

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)
• 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)

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
• 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

“The RHO mutation affects more than 10,000 people in the US,” Dr. David Birch, Scientific Director, Retina Foundation of the Southwest and Principal investigator of the study, said in a company news release. “In my view, the clinical study update supports the gene-agnostic mechanism of action of OCU400 in RHO patients. The improvements in BCVA, LLVA and MLMT in this patient population are very exciting and encouraging because stabilization alone could be considered as a treatment benefit.”

The clinical study update from the phase 1/2 clinical trial demonstrated that OCU400 continued to be generally safe and well-tolerated in subjects across different mutations and dose levels. There were no serious adverse events (SAEs) related to the investigational product in the low and medium-dose cohorts. In the high-dose and open-enrollment cohorts, SAEs were reported for two subjects. Adverse events were mostly deemed related to the surgical procedure and resolved within a few days to weeks.

Ocugen said it will continue to monitor long-term safety and efficacy data from the treated patients and provide additional updates.