Ocugen Gene Therapies Progress in Stargardt, Retinitis Pigmentosa, and Geographic Atrophy


Ocugen’s gene agnostic modifier gene therapies include OCU400 and OCU410.

Benjamin Bakall, MD, PhD, Director of Clinical Research, Associated Retina Consultants, and Clinical Assistant Professor, University of Arizona, College of Medicine – Phoenix

Benjamin Bakall, MD, PhD

Credit: American Society of Retina Specialists

Ocugen has made progress in its gene therapy programs for Stargardt disease, retinitis pigmentosa, and geographic atrophy.

The company has announced that it completed dosing in cohort 2 of patients with Stargardt disease (SD) in the phase 1/2 GARDian trial (NCT05956626) of OCU410ST, received investigational new drug (IND) clearance for a phase 3 trial of OCU400 in patients with retinitis pigmentosa (RP), and is enrolling the next cohort of patients with geographic atrophy (GA) in the phase 1/2 ArMaDa trial (NCT06018558) of OCU410.1,2,3

OCU410 is an adeno-associated virus (AAV) vector gene therapy that delivers the RORA (RAR Related Orphan Receptor A) gene via unilateral subretinal administration. The Nuclear Hormone Receptor (NHR) RORA regulates pathways including lipofuscin formation, oxidative stress, compliment formation, inflammation, and cell survival networks. OCU410ST is the version being investigated for SD.

The GARDian trial has dosed 6 patients with SD so far and plans to dose an additional 3 patients in the high dose, third and final cohort in the dose-escalation phase with OCU410ST pending a Data and Safety Monitoring Board review of the 4-week safety data of the medium dose, second cohort. In its first phase, the GARDian trial is assessing safety and efficacy of 3.75×1010 vg/mL, 7.5×1010 vg/mL, and 2.25×1011 vg/mL doses, before proceeding to a randomized, dose-expansion study evaluating 2 selected doses.

READ MORE: NGGT Biotechnology’s Gene Therapy NGGT001 Improves Vision in Patients With Bietti’s Crystalline Dystrophy

“There remains a great unmet medical need for patients with SD, which is the most common inherited retinal disease affecting the center of the vision and does not have any FDA-approved treatment options. OCU410ST is a novel modifier gene therapy that provides hope to these patients,” Benjamin Bakall, MD, PhD, Director of Clinical Research, Associated Retina Consultants, and Clinical Assistant Professor, University of Arizona, College of Medicine – Phoenix, said in a statement.1 “I am excited that we completed dosing of the last patient in Cohort 2, who received medium dose of this novel therapeutic leveraging a gene-agnostic approach, at Associated Retina Consultants (ARC) in Phoenix, Arizona with the surgical team led by Dr. Mark Kwong, Medical Director of ARC.”

OCU400 is a gene-agnostic modifier gene therapy product based on the NHR gene, NR2E3, which regulates retinal functions including photoreceptor development and maintenance, metabolism, phototransduction, inflammation and cell survival networks.

The IND amendment enables Ocugen to initiate a phase 3 study with a sample size of 150 participants with RP — 1 arm of 75 participants with the RHO gene mutation and the other arm with 75 participants that are gene agnostic. Each arm will randomize participants to receive either 2.5 x 1010 vg/eye of OCU400 or control.

“We believe that the gene-agnostic clinical trial design provides an appropriate therapeutic option to include patients who have greater potential of benefiting from treatment,” Huma Qamar, MD, Chief Medical Officer, Ocugen, said.2 “We are looking forward to working with our selected trial sites and leading retinal surgeons to deliver this novel modifier gene therapy to potentially address unmet medical needs.”

The ArMaDa trial has dosed 3 participants with geographic atrophy (GA) in the Phase 1/2 clinical trial so far and plans to dose 3 additional participants in the medium dose, second cohort 2 and 3 patients in the high dose, third cohort of OCU410 in the dose-escalation phase.

“The DSMB has recommended moving forward to medium dose for dosing subjects with GA,” Peter Chang, MD, FACS, DSMB Chair for the OCU410 clinical trial, said.3 “No serious adverse events (SAEs) related to OCU410 have been reported to date. I believe that this marks a critical next step towards determining the optimal dosing regimen and an important milestone for the clinical development of OCU410.”

1. Ocugen Announces Dosing Completion of Subjects With Stargardt Disease In Cohort 2 Of Phase 1/2 GARDian Clinical Trial Of OCU410ST—A Modifier Gene Therapy. News release. Ocugen. May 15, 2024. https://ir.ocugen.com/news-releases/news-release-details/ocugen-announces-dosing-completion-subjects-stargardt-disease
2. Ocugen, Inc. Announces U.S. FDA Clearance of IND Amendment to Initiate OCU400 Phase 3 Clinical Trial — First Gene Therapy to Enter Phase 3 With a Broad Retinitis Pigmentosa Indication. News release. Ocugen. April 8, 2024. https://ir.ocugen.com/news-releases/news-release-details/ocugen-inc-announces-us-fda-clearance-ind-amendment-initiate/
3. Ocugen Announces Positive Data and Safety Monitoring Board Review and Initiation of Enrollment in Medium Dose for OCU410—a Modifier Gene Therapy—in Phase 1/2 ArMaDa Study for Geographic Atrophy. News release. Ocugen. April 5, 2024. https://www.globenewswire.com/news-release/2024/4/5/2858442/0/en/Ocugen-Announces-Positive-Data-and-Safety-Monitoring-Board-Review-and-Initiation-of-Enrollment-in-Medium-Dose-for-OCU410-a-Modifier-Gene-Therapy-in-Phase-1-2-ArMaDa-Study-for-Geogr.html
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