EMA's CHMP Gives Ocugen the Green Light to Submit MAA for OCU410ST Based on GARDian3 Trial

The European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) has provided Ocugen with a positive opinion regarding the use of data from the United States–based phase 2/3 GARDian3 clinical trial (NCT05956626) to support a marketing authorization application (MAA) for OCU410ST, an investigational adeno-associated virus (AAV) vector-based gene therapy, for the treatment of Stargardt disease.¹

The EMA’s decision was based on data from the phase 1 GARDian clinical trial (NCT05956626), in which evaluable treated eyes showed 48% slower lesion growth compared with untreated eyes at 12 months of follow-up. In addition, evaluable treated eyes showed improvement in best-corrected visual acuity (BCVA) of almost 2 lines or 9 letters compared with untreated eyes, a changed deemed clinically meaningful and statistically significant (P = .031).

“This positive opinion endorses a single trial as the basis for both biologics license application [BLA] and MAA submissions and brings us closer to providing a 1-time, modifier gene therapy to approximately 100,000 Stargardt patients in the United States and Europe combined,” Shankar Musunuri, PhD, the chairman, chief executive officer, and cofounder of Ocugen, said in a statement.¹ “We are very encouraged about the prospect of addressing the unmet medical need that exists for these patients who currently have no approved treatment options available to them.”

Notably, the first patient was dosed in the GARDian3 in July 2025.² The phase 2/3 trial will enroll 51 participants with Stargardt disease, and 34 of the patients will be treated with a 1-time subretinal injection of OCU410ST (200 μL at a concentration of 1.5 × 10¹¹ vector genomes/mL) in their worse-seeing eye, whereas 17 participants will act as untreated controls. The study’s primary end point is reduction in atrophic lesion size, with major secondary end points including improvements in BCVA and low-luminance visual acuity compared with controls.^1,2 In addition, GARDian3 will feature a masked interim analysis of 16 of the treated patients and 8 of the control group patients at the 8-month time point.

“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, said in a statement at the time the first patient’s dosing was announced.² “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.”

Notably, 1-year follow-up data from GARDian3 will be used to support both the planned BLA submission to the FDA and the planned MAA submission to the EMA.¹ Ocugen anticipates that GARDian3 will finish enrolling patients in the first quarter of next year and expects to file a BLA with the FDA in the first half of 2027.

In May 2025, OCU410ST was granted rare pediatric disease designation (RPDD) from the FDA for the treatment of ABCA4-associated retinopathies, including Stargardt disease, retinitis pigmentosa 19, and cone-rod dystrophy 3.³ OCU410ST has previously been granted orphan drug designations for ABCA4-associated retinopathies by both the FDA and EMA.

“This latest designation for OCU410ST reaffirms the urgency of providing a therapeutic option to Stargardt patients who have no FDA-approved treatment available,” Musunuri said in a statement at the time of the RPDD designation announcement.³ “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.”

REFERENCES
1. Ocugen, Inc. announces positive scientific advice from the European Medicines Agency related to the approval pathway for OCU410ST—modifier gene therapy for Stargardt disease. News release. Ocugen Inc. August 13, 2025. Accessed August 14, 2025. https://ir.ocugen.com/news-releases/news-release-details/ocugen-inc-announces-positive-scientific-advice-european-0
2. Ocugen, Inc. announces first patient dosed in phase 2/3 GARDian3 pivotal confirmatory trial for OCU410st—novel modifier gene therapy candidate for Stargardt disease. News release. July 18, 2025. Accessed August 14, 2025. https://ir.ocugen.com/news-releases/news-release-details/ocugen-inc-announces-first-patient-dosed-phase-23-gardian3
3. 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 August 14, 2025. https://ir.ocugen.com/news-releases/news-release-details/ocugen-announces-rare-pediatric-disease-designation-granted