Ocugen Doses First Patient With Stargardt Disease With Gene Modifier Therapy


The company most recently reported data from a trial in retinitis pigmentosa and Leber congenital amaurosis demonstrating OCU400’s gene-agnostic mechanism of action.

Ocugen has dosed the first patient in its Phase 1/2 GARDian clinical trial (NCT05956626) for OCU410ST (AAV5-hRORA) a modifier gene therapy candidate being developed for Stargardt disease.1

“There is a significant unmet medical need for the approximate 35,000 patients in the U.S. living with Stargardt disease,” Shankar Musunuri, PhD, chairman, chief executive officer and cofounder, Ocugen, said in a statement.1 “It is critical to our mission to develop innovative treatments for inherited retinal diseases (IRDs) and this milestone is an important step in bringing our novel modifier gene therapies to people who desperately need them.”

Stargardt disease is a rare genetically inherited disease that affects the retina and often results in slow progressive vision loss in children and adults. OCU410ST is an adeno-associated virus therapy that uses the AAV5 vector to deliver the RORA (RAR Related Orphan Receptor A) gene.

The phase 1/2 trial will assess the safety and tolerability of unilateral subretinal administration of OCU410ST. The first phase is a multicenter, open-label, dose ranging study and the second will be a randomized, blinded, dose-expansion study in adult and pediatric participants assessing 2 OCU410ST dose groups or placebo.

READ MORE: REGENXBIO’s ABBV-RGX-314 Trials Aim to Reduce Treatment Burden in Inherited Retinal Diseases

“It is important and exciting to pursue novel therapies for untreatable blinding diseases,” Charles Wykoff, MD, PhD, Director of Research, Retina Consultants of Texas, added.1 “Initiation of this trial program investigating a new mechanism of action for the treatment of Stargardt disease is inspiring and brings hope to patients and families.”

Ocugen recently announced data from a phase 1/2 clinical trial (NCT05203939) evaluating OCU400, the company’s lead investigational ophthalmic program, in patients with retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA).2 Like OCU410ST, OCU400 uses the company’s modifier gene therapy approach based on Nuclear Hormone Receptor (NHR) RORA that regulates pathways linked to IRDs.

Among the 12 patients in the trial, 10 patients (83%) experienced stabilization or improvement from baseline in best-corrected visual acuity (BCVA) in their treated eyes as well as stabilization or improvement from baseline in low-luminance visual acuity (LLVA). Similarly, multiluminance mobility testing (MLMT) scores stabilized or improved from baseline in 9 patients (75%).2

OCU400 was deemed generally safe and well-tolerated across the study population. One patient who received the high dose and 1 patient included in the open enrollment cohort experienced serious adverse events, although the surgical procedure accounted for most AEs and most resolved within a few days to weeks.

“[With] traditional gene therapy, when you're giving a functional gene, you're not looking at the entire system. There's a lot coming out in epigenetics... [showing] there are other factors which impact degeneration. You can give a functioning gene, but maybe there is a cascading effect going on. So, if you don't have any photoreceptors left 5 years after you do gene therapy, which is supposed to be a one-time therapy for life, then it won't function, it won't work. So that's where we come in, our therapy resets the homeostasis, and provides a healthy environment for cells to survive. That's really important. So that's why we believe this is a way to go with a gene agnostic approach,” Musunuri told CGTLive.

1. Ocugen, Inc. announces first patient dosed in phase 1/2 clinical trial evaluating the safety and efficacy of OCU410ST—modifier gene therapy—for Stargardt Disease. News release. Ocugen. November 10, 2023. https://finance.yahoo.com/news/ocugen-inc-announces-first-patient-123000501.html
2. Ocugen announces positive clinical study update from the phase 1/2 trial of OCU400, a modifier gene therapy product candidate, for the treatment of retinitis pigmentosa (R) and Leber congenital amaurosis (LCA). News release. September 13, 2023. Accessed September 19, 2023. https://ir.ocugen.com/news-releases/news-release-details/ocugen-announces-positive-clinical-study-update-phase-12-trial
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