Ocugen's OCU400, a novel gene-agnostic modifier gene therapy, is showing promising results in treating retinitis pigmentosa (RP), a genetic disease causing progressive vision loss. Recent data from a Phase 1/2 clinical trial and regulatory milestones in Europe highlight the potential of OCU400 to address this unmet medical need.
Positive Phase 1/2 Trial Results
Data from the Phase 1/2 clinical trial of OCU400 demonstrated significant improvements in visual function for patients with RP. The 2-year update showed that all treated patients (9/9) experienced either improvement or preservation of visual function compared to their untreated eyes. Specifically, OCU400 led to a meaningful improvement of 2 lines (10 letters on the ETDRS chart) in low-luminance visual acuity (LLVA) in treated eyes compared to untreated fellow eyes (p=0.01). This statistically significant improvement was observed across all subjects, irrespective of the underlying genetic mutation, validating OCU400's gene-agnostic mechanism of action.
Syed M. Shah, MD, FACS, Vice Chair for Research and Digital Medicine, Director of Retina Service at Gundersen Health System, noted, "The broad spectrum of genes and mutations causing RP presents a unique challenge in developing treatments for this unmet need. This is where the promise of mutation-agnostic therapies becomes particularly compelling. OCU400’s demonstrated effectiveness across multiple mutations not only offers hope to RP patients but also opens new possibilities for treating other retinal diseases."
EMA's ATMP Classification
The European Medicines Agency (EMA) has granted OCU400 an Advanced Therapy Medicinal Product (ATMP) classification. This designation is reserved for medicines that offer groundbreaking opportunities for the treatment of diseases and accelerates the regulatory review timeline. The ATMP classification allows Ocugen to interact more frequently with the EMA for scientific advice and protocol assistance as the company pursues a Marketing Authorization Application (MAA) filing in 2026.
Dr. Shankar Musunuri, Chairman, CEO, and Co-founder of Ocugen, stated, "Receiving ATMP classification is another significant milestone toward bringing OCU400 to the market in Europe. This designation makes it possible to stay on track with our clinical and commercial strategy and potentially provide this novel modifier gene therapy candidate to all RP patients in the United States (U.S.) and Europe by 2027."
Ongoing Phase 3 liMeliGhT Clinical Trial
Ocugen is currently conducting the Phase 3 OCU400 liMeliGhT clinical trial, a pivotal study designed to support Biologics License Application (BLA) and MAA submissions in the U.S. and Europe. The trial is enrolling 150 participants, divided into two arms: one with RHO gene mutations and another that is gene-agnostic. Participants in each arm are randomized 2:1 to receive either OCU400 (2.5 x 10^10 vg/eye) or an untreated control. The company plans to file simultaneously in the U.S. and Europe upon completion of the Phase 3 trial, expected in the first half of 2026.
Addressing Unmet Needs in Retinitis Pigmentosa
Retinitis pigmentosa affects approximately 310,000 patients in the U.S., EU, and Canada. The disease is associated with mutations in over 100 genes, and currently, there are limited treatment options available that can effectively slow or stop its progression. OCU400, a gene-agnostic modifier gene therapy based on the NR2E3 gene, aims to address this unmet need by resetting altered cellular gene networks and establishing homeostasis in the retina.
Dr. Huma Qamar, Chief Medical Officer at Ocugen, expressed optimism about the EMA's recognition of OCU400 and the ongoing Phase 3 trial, stating, "I look forward to working collaboratively with the EMA to address the unmet medical need that remains for nearly 98% of the RP patient population."
Alternative Approaches
Nanoscope Therapeutics is also on the brink of filing for FDA approval of MCO-010 (sonpiretigene isteparvovec), a gene therapy for RP that can be used regardless of underlying genetic mutations. In the phase 2b RESTORE trial, a one-off administration of the gene therapy led to a clinically meaningful improvement in legally blind RP patients. Nanoscope plans to submit a dossier to the FDA later this year.
