First Patient Dosed in Phase 2/3 GARDian3 Trial of OCU410ST for Stargardt Disease

Ocugen has dosed the first patient in its phase 2/3 GARDian3 clinical trial (NCT05956626) evaluating OCU410ST (AAV5-hRORA), a novel modifier gene therapy candidate, for the treatment of Stargardt disease (ABCA4-associated retinopathies).¹ The trial marks a critical step forward in Ocugen’s strategy to bring a onetime therapy to patients with inherited retinal degenerative conditions.

“Dosing the first patient is an especially significant milestone and brings us closer to our goal of addressing the unmet medical need that exists for all patients [with] Stargardt [disease]: 100,000 in the US and Europe and 1 million worldwide,” Shankar Musunuri, PhD, chairman, CEO, and cofounder of Ocugen, said in a statement.¹

The phase 2/3 GARDian3 study follows positive findings from the phase 1 GARDian trial, which showed a 48% slower lesion growth at 12-month follow-up in treated eyes compared with untreated eyes. Treated eyes also demonstrated a statistically significant (P = .031) and clinically meaningful improvement of nearly 2 lines in best corrected visual acuity (BCVA).

“Initiating dosing in this pivotal phase 2/3 study is an important advancement for Ocugen and more importantly for the Stargardt community,” Huma Qamar, MD, MPH, chief medical officer of Ocugen, added to the statement.¹ “The adaptive design of this trial, including a masked interim analysis at 8 months on 24 subjects, enables us to efficiently evaluate early signals of efficacy and safety while optimizing study conduct.”

The phase 2/3 trial will enroll 51 participants with Stargardt disease. Thirty-four participants will receive a onetime subretinal injection of OCU410ST (200 μL at a concentration of 1.5 × 10¹¹ vector genomes/mL) in the worse-seeing eye, and 17 will serve as untreated controls. The primary end point is reduction in atrophic lesion size, with secondary end points including BCVA and low-luminance visual acuity. Ocugen plans to use 1-year follow-up data to support a biologics license application (BLA), targeted for 2027.

“Treating the first patient with this novel gene therapy in the GARDian3 trial is a proud and hopeful moment for our team and for families affected by Stargardt disease,” Victor H. Gonzalez, MD, principal investigator at Valley Retina Institute in McAllen, Texas, added to the statement.¹ “The encouraging phase 1 results give us confidence that OCU410ST could meaningfully slow disease progression and help preserve vision. This trial brings us closer to the possibility of a onetime gene therapy that could transform patients’ quality of life for years to come.”

To date, OCU410ST has shown a favorable safety and tolerability profile, with no serious adverse events or adverse events of special interest, such as ischemic optic neuropathy, vasculitis, intraocular inflammation, endophthalmitis, or choroidal neovascularization.

OCU410ST is Ocugen’s second late-stage clinical program and part of its broader modifier gene therapy platform, which uses adeno-associated virus vectors to deliver the RORA gene. The candidate targets multiple pathogenic pathways implicated in Stargardt disease, including oxidative stress, lipofuscin accumulation, inflammation, and complement dysregulation. RORA encodes a nuclear hormone receptor that regulates gene expression via hormone response elements and interacts with proteins involved in organ development and differentiation, functions that may be impaired in Stargardt disease. It may also play a role in circadian rhythm regulation, which may also contribute to its role in retinal homeostasis.²

This platform reflects a gene-agnostic strategy that aims to provide durable, broad-spectrum benefit for inherited retinal diseases.¹ “Progressing our second modifier gene therapy candidate into a registration clinical trial is a pivotal step in potentially providing a onetime therapy for life,” Musunuri said.¹ Stargardt disease, the most common form of inherited macular degeneration, is characterized by progressive loss of central vision, typically beginning in childhood or adolescence. Current management options are limited, with no approved therapies available to alter disease progression. Ocugen aims to file 3 BLAs over the next 3 years, with OCU410ST positioned as a leading candidate to address an area of significant unmet need in retinal degenerative disease.