Ocugen, Inc. recently announced that the first patient was dosed in the global phase 3 ArMaDa3 registrational trial of OCU410 for geographic atrophy (GA) secondary to dry age-related macular degeneration (AMD).
Let’s start with the company.
Ocugen is a biotechnology company focused on developing gene therapies via its breakthrough modifier gene therapy platform, which utilizes a gene-agnostic approach designed to address the underlying pathophysiology by restoring balance across multiple gene networks.
The company is currently evaluating four gene therapies (with the top three listed below in late-stage clinical trials) for inherited retinal diseases (IRD) and other causes of global blindness, including:
- Retinitis pigmentosa (OCU400)
- Stargardt disease (OCU410ST)
- GA (OCU410; the topic of this story)
- Diabetic macular edema, diabetic retinopathy, and wet AMD (OCU200)
Tell me more about OCU410.
The candidate is an investigational first-in-class modifier gene therapy.
What it does: delivers the human retinoid-related orphan receptor alpha (RORA) gene via a single unilateral subretinal injection to regulate multiple pathways implicated in the pathogenesis of GA:
- Complement activation
- Neuroinflammation
- Oxidative stress
- Lipid metabolism
And in recent news: In July, OCU410 received Regenerative Medicine Advanced Therapy (RMAT) designation from the FDA—as well as Advanced Therapy Medicinal Product classification from the European Medicines Agency's (EMA) Committee for Advanced Therapies.
Explain the significance of RMAT designation.
This is granted to regenerative medicine therapies intended to treat serious or life-threatening conditions where preliminary clinical evidence indicates the potential to address an unmet medical need.
For the OCU410 program, the designation provides:
- Eligibility for accelerated approval and priority review, which may reduce the time from Biologics License Application (BLA) submission to potential market entry
- All benefits of Breakthrough Therapy designation, including intensive FDA guidance on efficient development and organizational commitment involving senior FDA leadership
- Early and frequent FDA interactions on the use of surrogate and intermediate clinical endpoints reasonably likely to predict long-term clinical benefit-directly relevant to OCU410’s fundus autofluorescence (FAF)-based anatomic primary endpoint
- Potential flexibility in satisfying post-approval requirements, including through expanded patient registries or real-world evidence
How has OCU410 performed in previous trials?
The phase 3 trial and the RMAT designation were supported by 12-month data from the phase 2 ArMaDa trial (NCT06018558), a multicenter, randomized, controlled study of 51 subjects with GA secondary to dry AMD.
Key findings from the ArMaDa trial include:
- 31% reduction in GA lesion area growth rate in the medium dose group versus control at 12 months (p < 0.05) in the pivotal phase 3 population (lesion size of ≥ 2.5 mm2 and ≤ 17.5 mm2)
- 27% reduction in ellipsoid zone (EZ) area loss in the medium dose group versus control, measured via spectral domain optical coherence tomography (SD-OCT)
- In the medium dose group, approximately 20% of treated subjects showed no disease progression, and 75% demonstrated >30% reduction in lesion growth at 12 months.
Plus: No OCU410-related serious adverse events (SAEs) or adverse events of special interest (AESIs) have been reported to date.
Now tell me about the ArMaDa3 trial.
The phase 3 registrational study (NCT07770828) is a global, multicenter, randomized, controlled study enrolling 237 subjects with GA secondary to dry AMD in the United States, Canada, Europe, and Latin America.
The design: Participants are randomized 2:1 to a single 200 µL subretinal injection of OCU410 (5×1010 vg/mL) or an untreated control arm.
And the main outcome measures?
The primary endpoint is rate of change of square root-transformed GA lesion area (√mm²/year) by FAF at baseline, Month 4, Month 8, and Month 12, analyzed by mixed model for repeated measures (MMRM).
Secondary endpoints include:
- proportion of subjects with low-luminance visual acuity (LLVA) loss ≥15 ETDRS letters at two consecutive visits through Month 12
- rate of change of ellipsoid zone (EZ) area loss by SD-OCT
Expert opinion?
Although the United States is the only country with approved treatments for GA, Dr. Shankar Musunuri, PhD, Chairman, CEO, and co-founder of Ocugen, noted that complement inhibitors “address only one of the four disease pathways and require ongoing repeated eye injections.”
He added: “This is our third modifier gene therapy program to advance into late-stage development, demonstrating the strength of our platform and our vision for potentially delivering a one-time treatment for life.”
Lastly: When can we expect updates?
Ocugen reported that it intends to use data from the ArMaDa3 trial to support a BLA filing anticipated in 2028.