Evaluation of Safety And Efficacy Of Ocu400 Gene Therapy For Retinitis Pigmentosa: Phase 1/2 Study Results

Murthy Chavali

Ocugen Inc, USA

Biography :

Murthy Chavali brings over 20 years of experience in the biotechnology sector and academia, with a focus on innovation, discovery, drug development, and clinical research. Currently, he oversees the clinical development of various ophthalmological therapies at Ocugen, concentrating on conditions such as inherited retinal disor­ders, diabetic macular edema, and age-related macular degeneration. He has extensive experience in drug de­velopment, including expertise across a range of therapeutic modalities such as cell and gene therapies, small molecules, biologics, and stem cell therapies. His clinical development skills include creating Phase I-III clinical protocols, executing clinical trial studies, regulatory interactions and managing medical affairs teams.

Abstract :

Retinitis pigmentosa (RP) is a group of rare genetic disorders that causes retinal degenera­tion, leading to vision loss and blindness. Mutations in over 100 different genes can lead to RP, and the only FDA- approved gene therapy addresses merely 2% of cases, leaving most patients without therapeutic options. Gene-agnostic treatment approaches are viable alter­natives to traditional gene-specific therapies. Nuclear hormone receptor (NHR)-based novel modifier gene therapy utilizes NR2E3 overexpression as a gene- agnostic approach to mod­ulate retinal cell homeostasis through the regulation of multiple transcriptional networks. A total of 18 adult RP subjects with autosomal dominant or biallelic autosomal recessive NR2E3 mutations or autosomal dominant RHO mutations enrolled in the Phase 1/2, open-label clini­cal trial (NCT05203939). Subjects received a unilateral, single subretinal injection of OCU400 (AAV5- hNR2E3) with a low (5 x 109 vg/eye), medium (1 x 1010 vg/eye), or high (5 x 1010 vg/ eye) dose in the eye with poorer vision. The primary safety endpoints included identifying study-related adverse events and ophthalmological changes. Efficacy endpoints included changes from baseline in Best Corrected Visual Acuity (BCVA), Low-Luminance Visual Acuity (LLVA), and the Multi-Luminance Mobility Test (MLMT). After 12 months post-OCU400 dosing, analysis demonstrated that OCU400 treatment was safe and well tolerated. Efficacy results demonstrated stabilization or improvement in 89% (16/18) of subjects in the treated eye as assessed through BCVA or LLVA or MLMT compared to baseline. Importantly, 78% (14/18) of subjects displayed stabilization or improvement in MLMT scores. A Phase 3 clinical trial for OCU400 is ongoing (NCT06388200).