Ocugen announces positive clinical study update from the phase 1/2 trial of OCU400

Ocugen Inc. 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.

According to the company, 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 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.

Shankar Musunuri, MD, MBA, chairman, CEO, and co-founder of Ocugen, said in the news release the update supports the company’s 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,” he said in the news release.

The company noted in its news release the phase 1/2 trial is a multicenter, open-label, dose ranging study. A total of 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.

Moreover, according to the news release, Ocugen further expanded this phase1/2 trial to enroll LCA patients with CEP290 gene mutation and pediatric patients with NR2E3, RHO and CEP290 mutations.

Inherited retinal diseases (IRDs) such as RP and LCA encompass a group of genetic disorders that affect the retina, the light-sensitive tissue at the back of the eye. These diseases often lead to a gradual loss of vision over time and can ultimately result in blindness. Stabilization of vision is crucial for patients with IRDs due to the progressive and degenerative nature of these conditions.

Preserving remaining vision, slowing disease progression, or improving the vision can significantly impact patients’ quality of life. It not only enhances the quality of life for affected individuals but also provides hope for future treatments that may ultimately lead to vision restoration. Comprehensive care, early diagnosis, and access to emerging therapies are essential components of a strategy to stabilize vision in IRD patients.

Arun Upadhyay, PhD, chief scientific officer, head of Research, Development and Medical at Ocugen, said he is pleased to see the progress the company has made in its pursuit of developing a novel gene-agnostic therapy for RP and LCA.

“Our team’s unwavering dedication to advancing modifier gene therapy research

demonstrated positive preliminary clinical results that offer renewed hope to patients and their families,” Upadhyay said in the news release. “We remain resolute in our mission and vision to bring a bright future to those with inherited or age-related retinal diseases through courageous innovation and unwavering determination.”

OCU400 is in Phase 1/2 clinical trial for the treatment of Retinitis Pigmentosa (RP) and Leber congenital amaurosis (LCA). OCU400 is a novel modifier gene therapy treatment that targets nuclear hormone receptors to modulate gene expression within the retina and may help reset retinal homeostasis, potentially stabilizing cells and rescuing photoreceptor degeneration. OCU400 has the potential to be a gene-agnostic therapeutic for RP and LCA patients with inherited retinal degeneration.

Key results from the study update include:

Best Corrected Visual Acuity:

• 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 ³4-letter improvement and 33% (4/12) treated eyes experienced ³7-letter improvement in BCVA from baseline
• 57% (4/7) of RHO subjects’ treated eyes experienced ³4-letter improvement and 43% (3/7) treated eyes experienced ³7-letter improvement in BCVA scores from baseline

Low Luminance Visual Acuity:

• 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 ³5-letter improvement (1 line) in LLVA from baseline, with 25% (3/7) increasing by ³10 letters (2 lines)
• 43% (3/7) of RHO subjects experienced ³5-letter improvement (1 line) in treated eyes in LLVA scores from baseline, among which 29% (2/7) increased by ³10 letters (2 lines)

Multi Luminance Mobility Test:

• 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

This 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.

“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,” said Leila Vajzovic, MD< associate professor of ophthalmology with tenure, director of Duke, Vitreoretinal Fellowship Program at Duke Eye Center and Duke University School of Medicine and leader in gene-therapy research.

“The RHO mutation affects more than 10,000 people globally,” said David Birch, PhD, scientific director, Retina Foundation of the Southwest and Principal investigator of the study. “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 company noted 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.

“The clinical study update released by Ocugen appears to have a tangible biological impact on retinitis pigmentosa associated with NR2E3 and RHO mutations,” said David Boyer, MD, clinical professor of ophthalmology USC/Keck School of Medicine Los Angeles, CA and Partner, Retina Vitreous Associates Medical Group. “These findings may indicate a huge step forward in the way we approach and treat this condition. We remain optimistic and eager to continue the trial and understand the full potential of OCU400.”

According to the news release, Ocugen will continue to monitor long-term safety and efficacy data from the treated patients and provide additional updates.