Ocugen’s Gene Therapy OCU410ST Continues to Show Efficacy in Phase 1 Stargardt Disease Trial

This article was originally published on our sister site, NeurologyLive®.

Ocugen’s investigational adeno-associated virus (AAV)–based gene therapy OCU410ST demonstrated a +6-letter improvement in best-corrected visual acuity (BCVA) among BCVA-evaluable patients without confounders in the phase 1 GARDian1 clinical trial (NCT05956626).¹ These findings, along with additional study results, were published in Eye.

The BCVA analysis included 6 of the 9 patients treated in the study. At 12 months posttreatment, these patients experienced a mean improvement of +4.5 ± 2.20 ETDRS letters in treated eyes, compared with a decline of −1.5 ± 2.33 letters in untreated fellow eyes, corresponding to a net +6-letter gain. Investigators noted that visual acuity in all treated eyes was either stable (±4 letters) or improved (≥5 letters).

In addition, among 6 patients with gradable fundus auto fluorescence images, treated eyes showed 0.55 ± 0.27 mm² of atrophic lesion progression, compared with 0.19 ± 0.31 mm² in untreated eyes, representing a mean 54% reduction. Furthermore, for treated eyes, a 0.10 ± 0.039 mm/year annual √DDAF expansion occurred, whereas fellow eyes showed a 0.19 ± 0.026 mm/year annual √DDAF expansion, indicating a 50% decrease in lesion expansion. According to first author Arshad Khanani, MD, the director of clinical research and director of Fellowship at Sierra Eye Associates, and an Ocugen Scientific Advisory Board member, and colleagues, the expansion rate in treated eyes was below the 0.14–0.18 mm/year range reported in published natural history studies.

"The consistent benefits observed across both structural and functional endpoints including slowing atrophic lesion progression and stabilization or improvement in visual acuity highlight the potential of this modifier gene therapy platform approach to transform treatment outcomes for patients with Stargardt disease, who currently have no disease-modifying options available,” Khanani said in a press release.²

With regard to safety, there were no serious adverse events (AEs) or AEs of special interest deemed related to OCU410ST reported, and the treatment and surgical procedure were characterized as “well-tolerated”.¹ A total of 30 treatment-emergent AEs deemed unrelated to the gene therapy product were reported. These included grade 1 (73%) and grade 2 (27%) events and occurred across 8 of the 9 patients.

The group of treated patients in GARDian1 included 5 female patients and 4 male patients with a mean age of 41.7 ± 18.1 years. One of the patients, who was treated at the study’s high-dose, was lost to follow-up, but all other patients completed at least 12 months of follow-up.

OCU410ST is currently being evaluated in the the United States–based phase 2/3 GARDian3 clinical trial (NCT05956626).³ Notably, based on data from GARDian, in August 2025 the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) provided Ocugen with a positive opinion regarding the use of data from GARDian3 to support a marketing authorization application for the product in its jurisdiction.

"This publication in Eye validates the scientific approach and clinical promise of OCU410ST as a modifier gene therapy for Stargardt disease," Huma Qamar, MD, MPH, chief medical officer of Ocugen, added to the statement.² "The phase 1 GARDian1 trial demonstrated convergent functional and structural benefits. This represents a paradigm shift from any other approaches, including oral or mutation-constrained replacement approaches, to an agnostic modification strategy that can potentially benefit patients regardless of their underlying ABCA4 mutation with a potential single gene therapy for life. These results provide important support for our ongoing phase 2/3 GARDian3 trial."

REFERENCES
1. Khanani AM, Vajzovic L, Bakall B, Chavali VRM, Qamar H. A novel modifier gene therapy to treat Stargardt disease: Phase 1 GARDian1 Trial Insights. Eye. Published online January 10, 2026. doi:10.1038/s41433-025-04202-5
2. Ocugen announces publication of phase 1 GARDian1 trial results for OCU410ST modifier gene therapy. News release. Ocugen, Inc. January 12, 2026. Accessed January 29, 2026. https://ir.ocugen.com/news-releases/news-release-details/ocugen-announces-publication-phase-1-gardian1-trial-results
3. Ocugen, Inc. announces positive scientific advice from the European Medicines Agency related to the approval pathway for OCU410ST—modifier gene therapy for Stargardt disease. News release. Ocugen Inc. August 13, 2025. Accessed January 29, 2026. https://ir.ocugen.com/news-releases/news-release-details/ocugen-inc-announces-positive-scientific-advice-european-0