OCU400 Shows Benefit for Retinitis Pigmentosa in Phase 1/2 Data

One-year follow-up results in a Phase 1/2 clinical trial demonstrated the safety and efficacy of OCU400 gene therapy for the treatment of retinitis pigmentosa.

These data, presented at the American Society of Retina Specialists (ASRS) 42nd Annual Meeting, showed that 89% of participants experienced stabilization or improvement in efficacy endpoints, including best-corrected visual acuity (BCVA) and low-luminance visual acuity (LLVA).

“The study results show the potential benefit and gene-agnostic mechanism of action of OCU400, supporting continued development in later phase clinical trials,” said Benjamin Bakall, MD, PhD, Associated Retina Consultants.

Retinitis pigmentosa is a group of inherited retinal degenerations linked to mutations in >200 genes. Treatment is typically achieved by the delivery of a functional copy or knocking down disease-causing genes to supplement or restore its function.

A gene modifier therapy platform allows a novel therapeutic approach to reset the molecular clock by expression of the Nuclear Hormone Receptor, NR2E3, to treat retinitis pigmentosa with OCU400.

In pre-clinical findings, NR2E3 was shown to function as a modifier gene with therapeutic potential for retinitis pigmentosa. NRE23 delivery can improve retinal structure, function, and restore retinal homeostasis.

This study assessed the one-year safety and efficacy result of the OCU400 gene modifier therapy for retinitis pigmentosa linked to NR2E3 and RHO mutations.

The multi-center, open-labeled clinical trial was designed as a 3+3 dose escalation and expansion study.

Participants with mutations in biallelic autosomal recessive NR2E3, autosomal dominant NR2E3, or autosomal dominant RHO were treated with a single unilateral subretinal injection of OCU400. Three dose levels (5.0 x 109, 1.0 x 1010, or 5.0 x 1010 vg/eye) were administered in the study eye.

Safety endpoints included the assessment of safety, adverse events, ophthalmologic changes, and the assessment of immune and biochemical changes.

Efficacy endpoints involved BCVA, LLVA, and Multi-luminance Mobility Testing (MLMT). Exploratory endpoints included perimeters, electrophysiological, and NEI-VFQ-25 questionnaires.

Overall, 18 participants with retinitis pigmentosa completed the 12-month follow-up visits after OCU400 dosing.

An analysis at the end of the study suggested the relative safety and tolerability of OCU400. There were no serious adverse events (SAEs) correlated with OCU400 identified in either the low- or medium-dose cohorts.

For those in the high-dose and open-enrollment cohorts, two participants experienced SAEs. One was deemed related to surgical technique and the other to OCU400 and surgical technique.

Efficacy data showed stabilization or improvement in 89% (n = 16 of 18) of participants in treated eyes, assessed through BCVA, LLVA, or MLMT scores compared with baseline.

In particular, 78% (n = 14 of 18) of participants experienced stabilization or improvement in baseline MLMT scores. Notably, 80% (n = 8 of 10) of participants with RHO mutations experienced improvement.

_{Reference
Bakall B. One Year Follow-up in a Phase 1/2 Clinical Trial of a Gene Modifier Therapy (OCU400) for the Treatment of Retinitis Pigmentosa. Paper presented at the American Society of Retina Specialists (ASRS) 42nd Annual Meeting. Stockholm, Sweden. July 17-20, 2024.}