Slowing sight loss in stargardts: Ocugen’s gene therapy trial offers promising early results
Ocugen’s gene therapy candidate, OCU410ST, is an experimental treatment designed to slow vision loss in Stargardt disease, an inherited retinal disease (IRD) with no approved therapies currently.
What is Stargardt disease?
Stargardt disease is a progressive inherited retinal condition in which vision loss is caused by the death of photoreceptor cells (light-sensing cells) in the central portion of the retina called the macula. It is the most common form of juvenile macular dystrophy.
The condition is most commonly caused by mutations in the ABCA4 gene, which provides the instructions needed to make a protein found in the photoreceptor cells. This protein is responsible for transporting toxic byproducts, made by the regular visual cycle, away from photoreceptor cells. Without this protein, these toxins can accumulate over time on the macula, which we use for seeing fine detail in high definition, destroying light-sensing cells and central vision.
There are currently no treatments available for the condition, however, there are several therapeutic approaches in development, including OCU410ST by Ocugen.
What is OCU410ST?
OCU410ST uses a treatment approach known as modifier gene therapy. Researchers hope to use a gene called RORA to modify disease processes in the retina, rather than to fix a specific mutation in the ABCA4 gene. This means that this treatment approach has the potential to work for patients with various genetic mutations in the ABCA4 gene resulting in Stargardt disease.
The RORA gene makes a protein that helps to regulate what genes are turned on/off and can maintain cell health in the retina by influencing pathways linked to toxin build-up, cell damage and inflammation. The gene therapy uses an adeno associated viral vector (AAV) delivery method, meaning that a small virus, that doesn’t cause illness in humans, is used as a delivery system to introduce RORA within cells to alter genetic processes.
Phase 1 trial:
The Phase 1 trial, known as GARDian1, was a multicenter, open-label, dose escalation study involving 9 participants. The aim of this first in-human trial was to evaluate the safety, tolerability and early-efficacy of 3 doses of OCU410ST.
Findings:
GARDian1 demonstrated robust efficacy and safety outcomes supporting the clinical development of OCU410ST.
In Stargardt disease, certain areas of the retina get progressively damaged and die. This can be observed using a special imaging technique called Fundus Autofluorescence (FAF), where a light is shone into the eye and a camera captures images. These images provide a ‘map’ of how healthy the Retinal Pigment Epithelium (RPE) is, the retina’s supportive layer. Areas that glow normally suggest a healthy RPE, whereas areas that are darker can indicate cell damage or loss. These damaged areas are called areas of ‘atrophy’ or ‘atrophic lesions.’ By repeating FAF tests, doctors can track disease progression by comparing images to see if dark areas grow or if new ones appear. In Stargardt disease, increased atrophy means that the retina is progressively losing healthy cells, and as such vision progressively declines.
Among six patients with gradable FAF images, atrophic lesion growth was reduced by 54% in treated eyes, compared to untreated fellow eyes over 12 months. Lesion expansion was also 50% slower in treated eyes versus untreated eyes, below published natural history rates.
Other key findings include:
- In 6 participants who were able to have their vision measured using a best corrected visual acuity test, it was found that treated eyes were able to read about 5 more letters after 12-months compared to a 1 or 2 letter loss in untreated eyes. There were no other factors affecting vision.
- 100% of treated eyes either stabilized or improved in visual acuity
- No drug-related serious adverse events or adverse events of special interest were observed
“The consistent benefits observed across both structural and functional endpoints including slowing atrophic lesion progression and stabilization or improvement in visual acuity highlight the potential of this modifier gene therapy platform approach to transform treatment outcomes for patients with Stargardt disease, who currently have no disease-modifying options available. I am looking forward to the data read out from the ongoing Phase 2/3 GARDian3 trial.” – Dr. Arshad M. Khanani, lead author of the publication, Director of Clinical Research at Sierra Eye Associates, and Ocugen Scientific Advisory Board member.
What happens next – Phase 2/3 trial:
Ocugen are currently recruiting for their phase 2/3 trial of OCU420ST across 14 sites in the US. This trial is a randomized, outcome assessor-masked, multicentre study, that will enrol 51 participants. Participants will be enrolled in a 2:1 ratio to either the treatment group (n=34) or to an untreated control group (n=17).
This means that participants are randomly assigned to receive the treatment or the placebo, and the people who look at and measure the results don’t know which group each person was in. This helps to prevent their expectations from influencing how they judge the results.
The Phase 2/3 trial, known as GARDian3, is progressing ahead of schedule with anticipated enrolment completion in the first quarter of 2026.
To learn more about Ocugen please visit: Ocugen Inc. – Patient-Centric Biotechnology
To learn more about the phase 2/3 trial, please visit: Study Details | NCT05956626 | A Phase 2/3 Trial to Assess the Efficacy and Safety of OCU410ST for Stargardt Disease | ClinicalTrials.gov