Ocugen, Inc. announced that the U.S. Food and Drug Administration (FDA) has cleared the investigational new drug (IND) amendment to initiate a phase 2/3 pivotal confirmatory trial of OCU410ST, a modifier gene therapy candidate being developed for all Stargardt disease (ABCA4-associated retinopathies).
The FDA previously granted Rare Pediatric Disease Designation (RPDD) and Orphan Drug Designation for OCU410ST for the treatment of ABCA4-associated retinopathies including Stargardt disease, retinitis pigmentosa 19, and cone-rod dystrophy 3.
“We have had a highly productive and collaborative engagement with the FDA’s Center for Biologics Evaluation and Research (CBER) in establishing the pivotal confirmatory trial for OCU410ST,” said Shankar Musunuri, PhD, MBA, chairman, CEO and co-founder of Ocugen. “It’s evident that there is a real sense of urgency by the agency in providing treatment options for patients who currently have nothing available to them. As we initiate the phase 2/3 registration trial, we are expediting the clinical development of OCU410ST by two to three years and potentially providing an innovative gene therapy to patients desperate for a treatment option.”
Positive data from the phase 1 GARDian trial for OCU410ST demonstrated:
- A favorable safety and tolerability profile with no serious adverse events related to OCU410ST, including no cases of ischemic optic neuropathy, vasculitis, intraocular inflammation, endophthalmitis or choroidal neovascularization and no adverse events of special interest
- Considerably slower lesion growth—48% at 12-month follow up in evaluable treated eyes when compared to untreated eyes
- Statistically significant (p=0.031) improvement with clinically meaningful, nearly 2-line gain in visual function (BCVA) at 12-month follow-up in evaluable treated eyes when compared to untreated eyes
The phase 2/3 clinical trial for OCU410ST will enroll 51 participants diagnosed with Stargardt disease. Of these, 34 will receive a one-time subretinal injection of OCU410ST (200 μL at a concentration of 1.5 × 10¹¹ vector genomes/mL) in the eye with poorer visual acuity, while 17 will be assigned to an untreated control group.
The primary objective of the trial is to evaluate the reduction in atrophic lesion size. Key secondary endpoints include improvements in best corrected visual acuity (BCVA) and low luminance visual acuity (LLVA), compared to controls. Data from the one-year follow-up will be used to support the company’s Biologics License Application (BLA).
“The initiation of this pivotal Phase 2/3 study represents a significant milestone in our commitment to bringing transformative genetic therapies to individuals affected by Stargardt disease—a progressive and debilitating condition,” said Dr. Huma Qamar, chief medical officer at Ocugen. “The recent RPDD granted by the FDA for this program further underscores the urgent need for innovative treatment options for children living with Stargardt disease. OCU410ST, developed through our proprietary modifier gene therapy platform, is designed to target the underlying biological mechanisms of the disease.”
Approximately 100,000 patients in U.S. and Europe combined and 1 million patients globally live with Stargardt disease. Stargardt and ABCA4-associated retinopathies are genetically complex, involving more than 1,200 known mutations and addressing this condition with traditional gene therapy or gene editing approaches remains highly challenging.
“Stargardt disease represents a significant unmet medical need, particularly among children and young adults,” said Lejla Vajzovic, MD, FASRS, director of the Duke Surgical Vitreoretinal Fellowship Program and Professor of Ophthalmology, Pediatrics, and Biomedical Engineering with Tenure at Duke University Eye Center. “The phase 2/3 study of OCU410ST is thoughtfully designed with scientific rigor and a patient-centered focus to evaluate both structural and functional outcomes. We are optimistic that this approach will move us closer to a meaningful therapeutic solution for affected families.”
The OCU410ST phase 2/3 pivotal confirmatory trial represents a major advancement as Ocugen’s second late-stage clinical program. Ocugen plans to submit a BLA for OCU410ST in 2027 in alignment with its strategic goal of filing three BLAs over the next three years.
About OCU410ST
OCU410ST utilizes an AAV delivery platform for the retinal delivery of the RORA (RAR-Related Orphan Receptor A) gene. It represents Ocugen’s modifier gene therapy approach, which is based on Nuclear Hormone Receptor (NHR) RORA that regulates pathophysiological pathways linked to Stargardt disease, such as lipofuscin formation, oxidative stress, complement formation, inflammation, and cell survival networks.