Ocugen’s Gene Therapy OCU410ST Nets Rare Pediatric Disease Designation for ABCA4-Associated Retinopathies

Ocugen has received rare pediatric disease designation from the FDA for OCU410ST, an investigational adeno-associated virus (AAV) vector-based gene therapy, for the treatment of ABCA4-associated retinopathies, including Stargardt disease, retinitis pigmentosa 19, and cone-rod dystrophy 3.¹

Alongside the announcement, Ocugen noted that it intends to initiate a phase 2/3 confirmatory clinical trial for OCU410ST in the coming weeks and that it anticipates submitting a biologics license application (BLA) for the therapy to the FDA in 2027. OCU410ST has previously been granted orphan drug designations for ABCA4-associated retinopathies by both the FDA and European Medicines Agency (EMA).

“This latest designation for OCU410ST reaffirms the urgency of providing a therapeutic option to Stargardt patients who have no FDA-approved treatment available,” Shankar Musunuri, PhD, the chairman, chief executive officer, and cofounder of Ocugen, said in a statement.¹ “This inherited retinal disease presents itself most often in childhood—making Stargardt disease a diagnosis that not only affects the patient but impacts the entire family.”

OCU410, which uses an AAV5 vector, is based on Ocugen’s modifier gene therapy platform and delivers the RORA (RAR Related Orphan Receptor A) gene via unilateral subretinal administration.^2-4 The Nuclear Hormone Receptor (NHR) RORA regulates pathways including lipofuscin formation, oxidative stress, compliment formation, inflammation, and cell survival networks.

Notably, in March 2025 OCU410STreceived a positive opinion from the EMA and its Committee for Advanced Therapies (CAT), along with another of Ocugen’s gene therapies, OCU410, which is under evaluation for the treatment of vision loss due to geographic atrophy associated with dry age-related macular degeneration.⁵ Furthermore, according to Ocugen, the EMA has granted OCU410 and OCU410ST advanced therapy medicinal product classification. The designation allows for an accelerated timeline for regulatory review, in addition to scientific guidance and protocol assistance provided by the EMA.

The week before receiving the positive opinion from the EMA, Ocugen came into alignment with the FDA with plans for the phase 2/3 confirmatory trial for OCU410ST.⁶ As planned, the phase 2/3 trial will randomly assign 34 patients to be treated with a single, subretinal, 200-μL 1.5x10¹¹ vector genomes (vg)/mL dose of OCU410ST in their eye with worse visual acuity and 17 participants to an untreated control group. Change in atrophic lesion size will constitute the study’s primary end point, and best corrected visual acuityand low luminance visual acuity compared to untreated controls will serve as secondary end points. The planned BLA submission will utilize data from a 1 year time point.

“Getting approval for a phase 2/3 trial is a pivotal milestone, as this approach has never been explored in clinical trials for Stargardt disease,” Lejla Vajzovic, MD, FASRS, the director of the Duke Surgical Vitreoretinal Fellowship Program, and a professor of ophthalmology, pediatrics and biomedical engineering with tenure, adult and pediatric vitreoretinal surgery and disease at Duke University Eye Center, and a retina scientific advisory board chair for Ocugen, said in a February 2025 statement.⁶ “The FDA’s decision underscores the potential of OCU410ST to meet a critical unmet medical need for the approximately 44,000 Stargardt patients in the United States.”

OCU410ST is currently being evaluated for Stargardt disease in the phase 1/2 GARDian clinical trial (NCT05956626). Notably, in October 2024, the trial’s data and safety monitoring board (DSMB) gave Ocugen the green light to move onto the phase 2 portion of the study.²

“The DSMB has recommended moving forward with phase 2 enrollment, as safety data indicates that OCU410ST appears to be safe and well-tolerated to date,” lead study investigator Charles Wykoff, MD, PhD, the director of research at Retina Consultants of Texas & Retina Consultants of America, said in a statement at the time.² “The safety and tolerability profile of OCU410ST remains encouraging as the clinical trial has progressed and continues to bring hope to patients with Stargardt disease, which still has no FDA-approved treatments.”

REFERENCES
1. Ocugen announces rare pediatric disease designation granted for OCU410ST—modifier gene therapy for the treatment of Stargardt disease. News release. Ocugen, Inc. May 27, 2025. Accessed May 28, 2025. https://ir.ocugen.com/news-releases/news-release-details/ocugen-announces-rare-pediatric-disease-designation-granted
2. Data and safety monitoring board approves initiation of phase 2 of OCU410ST GARDian clinical trial for Stargardt disease. News release. Ocugen, Inc. October 22, 2024. Accessed May 28, 2025. https://ir.ocugen.com/news-releases/news-release-details/data-and-safety-monitoring-board-approves-initiation-phase-2
3. Ocugen Announces Dosing Completion of Subjects With Stargardt Disease In Cohort 2 Of Phase 1/2 GARDian Clinical Trial Of OCU410ST—A Modifier Gene Therapy. News release. Ocugen. May 15, 2024. Accessed May 28, 2025. https://ir.ocugen.com/news-releases/news-release-details/ocugen-announces-dosing-completion-subjects-stargardt-disease
4. Ocugen Announces Positive Data and Safety Monitoring Board Review and Initiation of Enrollment in Medium Dose for OCU410—a Modifier Gene Therapy—in Phase 1/2 ArMaDa Study for Geographic Atrophy. News release. Ocugen. April 5, 2024. Accessed May 28, 2025. https://www.globenewswire.com/news-release/2024/4/5/2858442/0/en/Ocugen-Announces-Positive-Data-and-Safety-Monitoring-Board-Review-and-Initiation-of-Enrollment-in-Medium-Dose-for-OCU410-a-Modifier-Gene-Therapy-in-Phase-1-2-ArMaDa-Study-for-Geogr.html
5. Ocugen Announces Positive Opinion of EMA’s Committee for Advanced Therapies for ATMP Classification for Novel Modifier Gene Therapy Candidate OCU410 for Geographic Atrophy and OCU410ST for Stargardt Disease. Ocugen. Press release. Published March 3, 2025. Accessed May 28, 2025. https://www.globenewswire.com/fr/news-release/2025/03/03/3035695/0/en/Ocugen-Announces-Positive-Opinion-of-EMA-s-Committee-for-Advanced-Therapies-for-ATMP-Classification-for-Novel-Modifier-Gene-Therapy-Candidate-OCU410-for-Geographic-Atrophy-and-OCU4.html
6. Ocugen, inc. announces FDA alignment on phase 2/3 pivotal confirmatory clinical trial for modifier gene therapy candidate OCU410ST for Stargardt disease. News release. Ocugen, Inc. February 27, 2025. Accessed May 28, 2025. https://mjhassoc.sharepoint.com/sites/GeneTherapyLive/_layouts/15/doc.aspx?sourcedoc={b197225b-8020-49f5-9568-317dc3ba3022}&action=edit