Ocugen, Inc. had dosing successfully completed ahead of schedule in the Phase 2/3 GARDian3 pivotal confirmatory clinical trial for OCU410ST (AAV5-hRORA)?a modifier gene therapy candidate developed for all Stargardt disease (ABCA4-associated retinopathies). GARDian3 trial enrollment and dosing completed (N=63) in less than nine months. Topline results expected in Second Quarter 2027 with BLA to follow by mid-2027.
OCU410ST represents a potential first-in-class, one-time modifier gene therapy for all ABCA4-associated retinopathies. GARDian3 is a multicenter, randomized, masked, pivotal Phase 2/3 confirmatory study designed to evaluate the efficacy and safety of OCU410ST in patients with all mutations of Stargardt disease. OCU410ST is administered as a single subretinal injection, leveraging Ocugen?s AAV5-based modifier gene therapy platform to provide durable expression of hRORA in the retina with the goal of slowing or halting progressive macular degeneration and preserving visual function.
The Phase 2/3 study enrolled 63 participants diagnosed with Stargardt disease. Subjects randomized to treatment group received a one-time subretinal injection of OCU410ST (3 × 10^10 vector genomes/eye) in the eye with poorer visual acuity, while untreated control group did not receive any treatment. The primary objective of the trial is to evaluate the reduction in atrophic lesion size at 12 months.
Key secondary endpoints include improvements in best corrected visual acuity (BCVA) and low luminance visual acuity (LLVA), compared to controls. Observational endpoints include preservation of Ellipsoid Zone (EZ) that correlates to visual function. While demonstrating functional benefit via visual acuity within 12 months can be challenging due to the disease?s natural history, it is believed that preservation of EZ will serve as a meaningful and early indicator of therapeutic benefit.
Interim analysis will be performed in the third quarter of 2026 when 24 subjects complete the 8-month follow-up visit post-OCU410ST treatment. Data from the one-year follow-up will be used to support the company?s planned Biologics License Application (BLA). OCU410ST maintains a favorable safety and tolerability profile with no serious adverse events or adverse events of special interest, including ischemic optic neuropathy, vasculitis, intraocular inflammation, endophthalmitis or choroidal neovascularization.
The OCU410ST Phase 2/3 pivotal confirmatory trial represents Ocugen?s second late-stage clinical program. Ocugen plans to submit the BLA for OCU410ST mid-2027 in alignment with its strategic goal of filing three BLAs by 2028. OCU410ST utilizes an AAV5 delivery platform to deliver the RORA (RAR-Related Orphan Receptor A) gene to the retina.
By restoring nuclear hormone receptor signaling, OCU410ST addresses pathophysiological pathways linked to Stargardt disease, including lipofuscin formation, oxidative stress, complement activation, inflammation, and photoreceptor survival networks independent of the underlying ABCA4 genotype. In a 12-month Phase 1 (GARDian 1) trial, evaluable treated eyes showed a 54% reduction in atrophic lesion growth versus untreated fellow eyes, with slower lesion expansion and improvement in visual acuity among evaluable patients. Treated eyes gained an average of 6 letters in BCVA, while untreated fellow eyes declined by 1.5 letters, and all treated eyes either stabilized or improved in visual acuity.
In evaluable subjects ellipsoid zone (EZ) loss rate was 116% slower in OCU410ST-treated eyes vs untreated fellow eyes at 12 months. Data indicates preservation or stabilization of photoreceptor integrity in treated eyes. No drug-related serious adverse events or adverse events of special interest were observed.
Stargardt disease type 1 is a genetic eye disorder caused by biallelic mutations in the ABCA4 gene. This condition leads to progressive macular degeneration, with onset typically occurring during childhood or adolescence. Affected patients experience progressive central vision loss while peripheral vision is usually preserved.
There are currently no FDA-approved treatments for this orphan indication.
