Ocugen doses first patient in Phase 3 liMeliGhT clinical trial for OCU400

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Ocugen Inc announced the first patient has been dosed in its Phase 3 liMeliGhT clinical trial for OCU400—a modifier gene therapy product candidate being developed for retinitis pigmentosa (RP).

“Each clinical milestone achieved by OCU400 brings us closer to providing a one-time treatment for life to patients living with RP,” Shankar Musunuri, PhD, MBA, chairman, CEO and Co-founder of Ocugen, said in a news release. “Dosing the first patient is especially significant and makes our dedication to serving RP patients—300,000 in the U.S. and Europe and 1.6 million worldwide—more tangible.”

According to the company, the Phase 3 liMeliGhT clinical trial comes on the heels of positive Phase 1/2 OCU400 data that suggests positive trends in best-corrected visual acuity (BCVA) and multi-luminance mobility testing (MLMT), and low-luminance visual acuity (LLVA) among treated eyes.

According to the company, OCU400 is a gene-agnostic modifier gene therapy product based on nuclear hormone receptor (NHR) gene, NR2E3. NR2E3 regulates diverse physiological functions within the retina—such as photoreceptor development and maintenance, metabolism, phototransduction, inflammation and cell survival networks. Through its drive functionality, OCU400 resets altered/affected cellular gene networks and establishes homeostasis—a state of balance, which has the potential to improve retinal health and function in patients with RP.¹

Moreover, 89% (16/18) of RP patients demonstrated preservation or improvement in the treated eye either on BCVA or LLVA or MLMT scores from baseline. The investigators also noted 80% (8/10) of RHO mutation subjects experienced either preservation or improvement in MLMT scores from baseline. Further, 78% (14/18) of subjects demonstrated preservation or improvement in treated eyes in MLMT scores from baseline.

The Phase 3 study will last for 1 year and include 150 participants—one arm of 75 participants with RHO gene mutations and the other arm with 75 participants that are gene agnostic. In each arm, the participants will be randomized 2:1 to the treatment group (2.5 x 1010 vg/eye of OCU400) and untreated control group, respectively. Patients 8 years of age and older, with early through late-stage advancement of RP, are being recruited to participate in the liMeliGhT study.

Luminance Dependent Navigation Assessment (LDNA)—a more sensitive and specific measurement of function than MLMT used in previous Phase 3 clinical trials—is the primary endpoint for the study. The Phase 3 liMeliGhT study will focus on the proportion of responders, in treated and untreated groups, achieving an improvement of at least 2 Lux levels from baseline in the study eyes.

Lejla Vajzovic, MD, FASRS, Director, Duke Surgical Vitreoretinal Fellowship Program, Associate Professor of Ophthalmology with Tenure Adult and Pediatric Vitreoretinal Surgery and Disease, Duke University Eye Center, and Retina Scientific Advisory Board Chair of Ocugen, noted that patients diagnosted with RP associated with mutations in multiple genes currently have no therapeutic options.

“As a retinal surgeon, I am encouraged by the therapeutic potential of OCU400 to provide long-term benefit to RP patients,” Vajzovic said in the news release. “OCU400 is a novel modifier gene therapy approach that could initiate a paradigm shift in the treatment of RP and to field of ophthalmology.”

Benjamin Bakall, MD, PhD, director of Clinical Research at Associated Retina Consultants (ARC) and Clinical Assistant Professor at University of Arizona, College of Medicine – Phoenix, noted the current Phase 3 trial for OCU400 offers hope for thousands of patients diagnosed with RP.

“I am encouraged that we may have a potential treatment option to preserve or improve the vision in RP patients regardless of gene mutation, and very pleased that the first patient dosing in the Phase 3 liMeliGhT clinical trial was performed at ARC,” he said in the news release.

Huma Qamar, MD, MPH, chief medical officer of Ocugen, noted that the company is grateful for its continued collaboration with Bakall and the team at ARC.

“We are excited to expand our enrollment to include more centers and patients representing a diverse array of RP gene mutations, which will be a validation of this novel gene therapy platform,” he said in the news release. “We will provide updates as our progress continues."

Ocugen previously announced that OCU400 has received orphan drug and RMAT designations from the FDA and that the EMA provided acceptability of the US-based trial for submission of a Marketing Authorization Application (MAA). With the first dosing of the Phase 3 clinical trial, OCU400 remains on track for the 2026 BLA and MAA approval targets.¹

Modifier gene therapy is designed to fulfill unmet medical needs related to retinal diseases, including IRDs, such as RP, LCA and Stargardt disease, as well as multifactorial diseases like dry age-related macular degeneration (dAMD).

Ocugen noted in the news release its gene therapy platform is based on the use of NHRs, master gene regulators, which have the potential to restore homeostasis — the basic biological processes in the retina.

Currently, the company has 3 modifier gene therapy programs in the clinic: OCU400, OCU410, and OCU410ST. In addition to the OCU400 Phase 3 liMeliGhT clinical trial, the OCU410 Phase 1/2 ArMaDa clinical trial for geographic atrophy (GA) secondary to dAMD and the OCU410ST Phase 1/2 GARDian clinical trial for Stargardt disease are currently underway. GA affects approximately two to three million people in the U.S. and EU combined and Stargardt disease affects nearly 100,000 people in the U.S. and EU combined.¹

Reference:

1. Ocugen. Ocugen, Inc. Announces First Patient Dosed in Phase 3 liMeliGhT Clinical Trial for OCU400—First Gene Therapy in Phase 3 with a Broad Retinitis Pigmentosa Indication. GlobeNewswire News Room. Published June 20, 2024. Accessed June 20, 2024. https://url.us.m.mimecastprotect.com/s/snfNC5ygrgTwQlQ7UznmUo?domain=globenewswire.com