Ocugen's OCU400, a novel gene therapy, is showing promising results in treating inherited retinal diseases (IRDs) like retinitis pigmentosa (RP). The therapy, currently in a Phase 3 clinical trial, takes a gene-agnostic approach, potentially overcoming the challenges posed by the vast genetic heterogeneity of RP.
Addressing Unmet Needs in Inherited Retinal Diseases
Inherited retinal diseases, including RP, present a significant unmet medical need. RP, affecting approximately 1 in 4000 individuals globally, leads to progressive vision loss, often resulting in blindness. While gene therapies exist, such as those targeting the RP65 gene, they address only a small fraction (1-2%) of the RP patient population. The challenge lies in the fact that over 100 genes are associated with RP, making individualized gene therapy development a daunting task.
OCU400: A Gene-Agnostic Approach
OCU400 distinguishes itself by modifying the underlying disease pathway rather than targeting specific gene mutations. This "Modifier Gene Therapy" approach aims to enhance photoreceptor function and preserve surviving retinal cells. The therapy involves a single subretinal injection targeting the NR2E3 gene.
Phase 1/2 Trial Results
Data from the Phase 1/2 trial, presented at the 24th EURETINA Congress, demonstrated that OCU400 was generally safe and well-tolerated across different mutations and dose levels in RP and LCA patients. In the RP cohort, nearly 90% of patients experienced stabilization or improvement in best-corrected visual acuity (BCVA) after OCU400 treatment. Furthermore, approximately 60% of intent-to-treat patients showed improvement in a luminance-dependent navigation assessment, the primary endpoint for the Phase 3 study.
Phase 3 Trial Design
The ongoing Phase 3 trial (liMeliGhT; NCT06388200) is a randomized, controlled study designed to evaluate the safety and efficacy of OCU400 in RP patients. The trial consists of two arms: a RHO-associated RP arm and a gene-agnostic arm. A total of 150 patients, including adults and children at different stages of the disease, will be enrolled and randomized in a 2:1 ratio to receive either OCU400 or remain as an untreated control. The primary efficacy endpoint is the Luminance Dependent Navigation Assessment (LDNA), measuring patient mobility under different light conditions. Treatment success is defined as an improvement of 2 lux levels or more from baseline after 12 months of treatment.
Regulatory Milestones and Future Directions
OCU400 has received orphan drug designation from both the FDA and the European Medicines Agency (EMA) for the treatment of RP and LCA. It has also been granted regenerative medicine advanced therapy designation from the FDA. Ocugen anticipates completing patient enrollment in the Phase 3 trial early next year and is preparing for a biologics license application (BLA) in 2026.
Ocugen is also developing OCU410, another modifier gene therapy targeting RORA, for geographic atrophy (GA) and Stargardt disease. Phase 1/2 clinical trials for OCU410 in these indications are underway, with preliminary data expected in the near future.
