FDA Clears Ocugen's OCU410ST Trial for Stargardt Disease

Ocugen has received clearance from the U.S. Food and Drug Administration (FDA) to initiate a Phase 2/3 pivotal confirmatory trial of OCU410ST, following approval of an Investigational New Drug (IND) amendment. This advancement marks a significant step toward a potential treatment for Stargardt disease and other ABCA4-related retinopathies.

OCU410ST: Gene Therapy Targeting Stargardt Disease

OCU410ST utilizes an adeno-associated virus (AAV) delivery platform to administer the RORA gene, which plays a critical role in modulating several key disease mechanisms in Stargardt disease. These include lipofuscin accumulation, oxidative stress, complement activation, inflammation, and cell survival pathways.

The FDA has previously granted Rare Pediatric Disease Designation (RPDD) and Orphan Drug Designation to OCU410ST for treating ABCA4-associated retinopathies, including Stargardt disease, retinitis pigmentosa 19, and cone-rod dystrophy 3.

Phase 1 GARDian Trial: Promising Early Outcomes

The Phase 1 GARDian trial demonstrated positive initial results for OCU410ST:

• No serious adverse events were linked to the therapy. There were no cases of ischemic optic neuropathy, vasculitis, intraocular inflammation, endophthalmitis, or choroidal neovascularization.

• Treated eyes exhibited a 48% reduction in lesion growth over 12 months compared to untreated eyes.

• A statistically significant (p=0.031) and clinically meaningful improvement of nearly two lines in best corrected visual acuity (BCVA) was observed at the 12-month follow-up.

Phase 2/3 Trial Design and Objectives

The upcoming Phase 2/3 trial will enroll 51 participants with Stargardt disease. Of these:

• 34 participants will receive a single subretinal injection of OCU410ST (200 μL at 1.5 × 10¹¹ vector genomes/mL) in the eye with poorer visual acuity.

•17 participants will serve as an untreated control group.

The primary endpoint of the trial is the reduction in atrophic lesion size. Key secondary endpoints include improvements in BCVA and low luminance visual acuity (LLVA).

Dr. Lejla Vajzovic, Director of the Duke Surgical Vitreoretinal Fellowship Program, commented, “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.”

Strategic Progress and Future Milestones

Ocugen plans to submit a Biologics License Application (BLA) for OCU410ST in 2027, using one-year follow-up data from the Phase 2/3 trial to support the filing.

Dr. Shankar Musunuri, Chairman, CEO, and Co-founder of Ocugen, stated, “We have had a highly productive and collaborative engagement with the FDA’s CBER in establishing the pivotal confirmatory trial for OCU410ST. 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.”