IRD Gene Therapy OCU400’s Phase 1/2 Trial

This is the second part of an interview with Arun Upadhyay, PhD. For the first part, click here.

Arun Upadhyay, PhD

Ocugen is seeking to address inherited retinal diseases (IRDs) such as retinitis pigmentosa (RP) with its gene-agnostic Modifier Gene Therapy Platform, which is intended to circumvent the need to target the large number of genes implicated in various forms of these diseases. Currently, the company is evaluating OCU400, a gene therapy product based on this platform, in a phase 1/2 clinical trial (NCT05203939).

Following the presentation of results from this study at the 24th EURETINA Congress held September 19 to 22, 2024, in Barcelona, Spain, CGTLive® spoke with Arun Upadhyay, PhD, the chief scientific officer and head of research, development, and Medical at Ocugen, to get an overview of the key findings. Upadhyay also discussed a few of the company's other programs based on the platform.

CGTLive: What did Ocugen present at the EURETINA conference?

Arun Upadhyay, PhD: We do have our e-poster at EURETINA, where we presented our OCU400 phase 1/2 study design as well as the study results.

I would like to discuss a few regulatory milestones we have for this particular product, and also some of the the additional data around our OCU400 phase 1/2 trial. The OCU400 modifier gene therapy product has received several regulatory milestones and designations, such as orphan drug designation from the FDA and European Medicines Agency for the treatment of RP and Leber congenital amaurosis. We also have received regenerative medicine and advanced therapeutic designations from the FDA. Recently, we also received expanded access—the protocol was granted by the FDA for OCU400 for the treatment of broader RP patients, which allows for basically treating the patient outside the phase 3 trial parameters. This is a significant step, if you look at it from a regulatory perspective, because it not just gives us one regulatory milestone, but also it demonstrates validation of the modifier gene therapy approach in the broader RP patients.

So in the phase 1/2 study overall we treated a total of 18 RP patients and the safety and tolerability of OCU400 was excellent, actually. Generally it was safe and well-tolerated in the study. That was the basis for us taking this product to the phase 3, in addition to our phase 1/2 efficacy data. As I mentioned, if you look at the phase 1/2 efficacy outcome, close to 60% of intent to treat patients derived from our phase 1/2 study responded on our primary end point, which we are using in the phase 3 study. In addition to our primary end point, which is based on a mobility course, we also assessed other parameters, like best corrected visual acuity and visual acuity under low light conditions, like low luminance visual acuity. On those parameters as well, patients either saw stabilization or improvement following the treatment compared to the untreated eye.

Is there anything else you would like to add?

I would like to highlight that currently we are enrolling patients in our OCU400 phase 3 study... It is for a broader indication, and this is the first of its own kind of trial in this space. No other company to our knowledge is running a broader RP designation trial. This trial has a potential to provide benefit to the larger patient population within this rare disease category—close to more than 100,000 patients. In addition, we are also running this trial in Lebel congenital amaurosis patients, and we are hoping to have some preliminary data available sometime soon that will help us in making decisions to take this program to the next phase of development, as well.

In addition to that, we have another program in our modifier gene therapy technology space. That is OCU410. It is based on another modifier gene: RORA. That product we are developing for 2 different indications. The first one is geographic atrophy (GA), that is the advanced stage of age-related macular degeneration.The other is a genetic disorder that is due to the ABC4 gene mutation that is called Stargardt disease.

Currently, these 2 program OCU410 for GA and OCU410 Stargardt are both in the phase 1/2 clinical stage. We completed the phase 1 portion of both studies, so we have completed dose escalation for both. So far, the safety and tolerability profile of these 2 products in these 2 patient populations looks good. For GA, right now we are enrolling patients in the phase 2 portion of the study. We will be providing some preliminary safety and efficacy data for both the GA and Stargardt trials sometime soon, in the near future. Regarding OCU400, we are targeting to complete the patient enrollment early next year and getting ready for a biologics license application in 2026.

This transcript has been edited for clarity.

REFERENCES
1. Ocugen, Inc. Announces First Patient Dosed in Phase 3liMeliGhT Clinical Trial for OCU400—First Gene Therapy in Phase 3 with a Broad Retinitis Pigmentosa Indication. June 20, 2024. Accessed October 7, 2024. https://www.globenewswire.com/news-release/2024/06/20/2901513/0/en/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.html