Ocugen Gets Green Light to Move Onto Phase 2 Portion of Trial Evaluating Stargardt Gene Therapy OCU410ST
The DSMB’s decision was made with reference to safety data from the GARDian trial’s phase 1 portion.
Ocugen has received clearance from a Data and Safety Monitoring Board (DSMB) to move onto the phase 2 portion of the phase 1/2GARDian clinical trial (NCT05956626), which is evaluating OCU410ST, an investigational adeno-associated virus (AAV) vector-based gene therapy, for the treatment of Stargardt disease.1
The DSMB’s decision was made with reference to safety data from the trial’s phase 1 portion, in which 9 patients were treated with the gene therapy at 1 of 3 doses: low (3.75x1010 vg/mL), medium (7.5x1010 vg/mL), or high (2.25x1011 vg/mL). Notably, no serious adverse events occurred among the treated patients. The DSMB determined that the high dose, which constitutes the maximum tolerated dose, and the medium dose may be used in the phase 2 portion of GARDian.
“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,” lead study investigator Charles Wykoff, MD, PhD, the director of research at Retina Consultants of Texas & Retina Consultants of America, said in a statement.1 “The safety and tolerability profile of OCU410ST remains encouraging as the clinical trial has progressed and continues to bring hope to patients with Stargardt disease, which still has no FDA-approved treatments.”
OCU410, which uses an AAV5 vector, is based on Ocugen’s modifier gene therapy platform and delivers the RORA (RAR Related Orphan Receptor A) gene via unilateral subretinal administration.1-3 The Nuclear Hormone Receptor (NHR) RORA regulates pathways including lipofuscin formation, oxidative stress, compliment formation, inflammation, and cell survival networks.
“We are enthusiastic about the potential of OCU410ST to be the first one-time novel modifier gene therapy for Stargardt disease,” Huma Qamar, MD, MPH, the chief medical officer of Ocugen, added to the statement.1 “We are encouraged by the prospect of addressing a substantial unmet medical need for the estimated 100,000 Stargardt patients in the United States and Europe.”
Notably, Ocugen is also developing OCU400, another AAV vector-based gene therapy based on the company’s modifier gene therapy platform, that is currently being evaluated in the phase 3 liMeliGhT clinical trial (NCT06388200) for the treatment of retinitis pigmentosa (RP).4 Following the dosing of the first patient in liMeliGhT in June 2024, Ocugen presented data from an earlier phase 1/2 clinical trial (NCT05203939) that evaluated OCU400 in RP and Leber congenital amaurosis at the 24th EURETINA Congress held September 19 to 22, 2024, in Barcelona, Spain. Across 18 patients treated in the study, OCU400 was generally safe and well-tolerated. In terms of efficacy, close to 60% of the intent-to-treat population responded to OCU400 with regard to a luminance dependent navigation assessment (LDNA). Notably, LDNA is being used as a primary end point in the phase 3 trial for OCU400. In light of this milestone, CGTLive® reached out to Arun Upadhyay, PhD, the chief scientific officer and head of research, development, and Medical at Ocugen, to learn more about the company’s approach.
“Unlike traditional gene therapies that target a specific mutation, our Modifier Gene Therapy approach basically aims to modify the underlying disease pathway affected by various mutations in these RP patients,” Upadhyay told CGTLive in the interview, which focused on OCU400. “Our approach is more gene-agnostic in nature, which not only enhances the function of the photoreceptor, but also helps with preserving the surviving retinal cells through cellular and molecular homeostasis.”
