Ocugen has received the go-ahead to proceed to Phase 2 of its Phase 1/2 GARDian clinical trial evaluating OCU410ST, a novel adeno-associated virus (AAV) vector-based gene therapy for Stargardt disease. The decision follows a review of Phase 1 safety data by the Data and Safety Monitoring Board (DSMB).
Favorable Safety Profile in Phase 1
The Phase 1 portion of the GARDian trial (NCT05956626) involved nine patients who received OCU410ST at one of three dose levels: low (3.75x1010 vg/mL), medium (7.5x1010 vg/mL), or high (2.25x1011 vg/mL). Encouragingly, no serious adverse events were reported across all treated patients. Based on these findings, the DSMB has recommended that both the high dose (maximum tolerated dose) and the medium dose be used in the Phase 2 portion of the study.
Addressing Unmet Needs in Stargardt Disease
"The DSMB has recommended moving forward with Phase 2 enrollment, as safety data indicates that OCU410ST appears to be safe and well-tolerated to date," stated Charles Wykoff, MD, PhD, lead study investigator and Director of Research at Retina Consultants of Texas & Retina Consultants of America. He further emphasized the significance of this advancement, noting that the therapy "continues to bring hope to patients with Stargardt disease, which still has no FDA-approved treatments."
Stargardt disease affects an estimated 100,000 individuals in the United States and Europe, highlighting the substantial unmet medical need that OCU410ST aims to address.
Mechanism of Action
OCU410ST leverages Ocugen’s modifier gene therapy platform, utilizing an AAV5 vector to deliver the RORA (RAR Related Orphan Receptor A) gene via unilateral subretinal administration. The Nuclear Hormone Receptor (NHR) RORA plays a crucial role in regulating pathways implicated in Stargardt disease pathology, including lipofuscin formation, oxidative stress, complement formation, inflammation, and cell survival networks.
Ocugen's Broader Pipeline
In addition to OCU410ST, Ocugen is also developing OCU400, another AAV vector-based gene therapy based on the same modifier gene therapy platform. OCU400 is currently in Phase 3 clinical trials (liMeliGhT trial, NCT06388200) for the treatment of retinitis pigmentosa (RP). Earlier Phase 1/2 data presented at the 24th EURETINA Congress showed that OCU400 was generally safe and well-tolerated in 18 patients with RP and Leber congenital amaurosis, with nearly 60% of patients responding positively in a luminance dependent navigation assessment (LDNA).
"We are enthusiastic about the potential of OCU410ST to be the first one-time novel modifier gene therapy for Stargardt disease," added Huma Qamar, MD, MPH, Chief Medical Officer of Ocugen.
