Breakthrough Clinical Results
Ocugen, Inc. announced positive scientific advice from the European Medicines Agency (EMA) regarding the approval pathway for OCU410ST, a modifier gene therapy for Stargardt disease. The EMA accepted a single U.S.-based Phase 2/3 clinical trial (GARDian3) for submission of a Marketing Authorization Application (MAA). This decision is based on the safety and tolerability data from the Phase 1 GARDian trial, showing a 48% slower lesion growth and a statistically significant improvement in visual acuity. The Phase 2/3 trial will enroll 51 participants, with data from the one-year follow-up supporting the BLA and MAA submissions. This positive opinion streamlines the regulatory process, potentially reducing time and cost for EU marketing authorization. OCU410ST uses an AAV delivery platform for the RORA gene, targeting pathways linked to Stargardt disease.
Key Highlights
- Positive scientific advice from the EMA for OCU410ST gene therapy for Stargardt disease.
- EMA accepted a single U.S.-based Phase 2/3 trial for MAA submission.
- Phase 1 data showed 48% slower lesion growth and significant visual acuity improvement.
- BLA filing anticipated in the first half of 2027.
Study Design Parameters
Study Design Parameters and Endpoints in Key Stargardt Disease Trials
Study Designs
- Multiple prospective and retrospective cohort studies have been conducted for Stargardt disease
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The ProgStar studies represent key research initiatives with both retrospective and prospective cohorts:
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Retrospective study: enrolled 251 patients (458 eyes) with 3.9±1.6 years mean follow-up
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Prospective study: enrolled 259 patients (489 eyes) with 6-month follow-up visits over a 2-year period
- A double-masked, randomized, placebo-controlled, crossover clinical trial evaluated docosahexaenoic acid (DHA) supplementation in 8 patients with Best disease
- A retrospective cohort study examined 71 patients with late-onset STGD1 (onset ≥45 years)
Inclusion Criteria
- ABCA4 gene mutations and specified ocular lesions were required for ProgStar studies
- Patients were aged 6 years and older
- In the retrospective ProgStar study, patients needed data from at least 2 and up to 4 visits
- The total observational period was at least 2 years and up to 5 years between visits
Primary Endpoints
- Visual acuity measured using Early Treatment Diabetic Retinopathy Study (ETDRS) charts
- Fundus autofluorescence (FAF) to assess areas of definitely decreased autofluorescence (DDAF)
- Spectral-domain optical coherence tomography (SD OCT) for retinal structure evaluation
- Microperimetry (MP) to measure retinal sensitivity
- In the DHA trial, primary outcomes included multifocal electroretinogram (mfERG) and electro-oculogram (EOG)
Secondary Endpoints
- Atrophy growth rates measured on FAF images
- Loss of external limiting membrane, ellipsoid zone, and retinal pigment epithelium (RPE) on OCT
- VF-14 scores and Humphrey visual fields in the DHA trial
- Time to foveal involvement in late-onset STGD1 study
- Plasma DHA levels in the DHA supplementation trial
Baseline Characteristics in ProgStar
- Retrospective study: 36% had no or mild visual acuity loss; 47% had DDAF areas (average 2.5±2.9 mm²)
- Prospective study: 20% had no or mild visual acuity loss; 64% had DDAF areas (average 4.0±4.4 mm²)
- Mean retinal sensitivity with MP was 10.8±5.0 dB
These studies provide critical insights into Stargardt disease progression and establish important endpoints for future interventional trials. The ProgStar studies represent the most comprehensive research initiatives to date, with their robust design and multiple assessment modalities providing valuable natural history data for this rare disease.
Incidence and Prevalence
Global Estimates of Stargardt Disease Incidence and Prevalence
Stargardt disease is recognized as one of the most frequent causes of macular degeneration in childhood. This condition is an autosomal recessive form of juvenile macular degeneration, primarily caused by mutations in the ABCA4 gene located on chromosome 1.
Genetic Basis
Research across different populations demonstrates the genetic basis of Stargardt disease: - A 2013 Mexican study of 31 patients found two ABCA4 mutant alleles in 64.5% of patients - A 2015 study showed 67% of patients had determined causes, with many having ABCA4 mutations - A 2021 Chinese study identified disease-causing variants in the ABCA4 gene in eight out of twelve families - A 2021 Indian cohort study reported ABCA4 gene mutations in over 80% of patients
Age of Onset
The median age at onset varies across populations: - In an Indian cohort, the median age at onset was 14 years (range: 5-49 years) - The median age at presentation was 22 years (range: 6-55 years) - Most patients in the Indian cohort "reported at a younger age compared to other populations"
Regional Data
Limited regional data is available from several studies: - A 2021 study from South India included 28 clinically diagnosed Stargardt-like phenotype patients - A 2019 study from Cleveland Clinic Abu Dhabi identified 22 Emirati patients (from 19 families) with ABCA4-related retinopathy between 2016-2018
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These included 11 males and 11 females
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First visual symptoms occurred between 5-33 years of age
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14 cases were childhood-onset (before 18 years)
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8 cases were adult-onset (at or after 18 years)
- A 2000 study examined 11 families from southern Italy, including 18 patients with STGD1
Global Prevalence
The available data suggests that Stargardt disease occurs across various ethnic groups with different mutation patterns, including Mexican, Chinese, Indian, French Canadian, and Emirati populations. Studies from Azerbaijan note that the prevalence rate of age-related macular degeneration (AMD) in available data is "many times lower than its actual prevalence (≥60‰)" but this refers to AMD, not specifically Stargardt disease.
The studies from different populations suggest that Stargardt disease has a global presence, though specific worldwide incidence rates or prevalence percentages are not provided in the current research data.
Drug used in other indications
No Information Available on OCU410ST Clinical Trials
No data is currently available regarding OCU410ST clinical trials for indications other than Stargardt disease. The requested information about alternative indications and intervention models for OCU410ST trials cannot be provided at this time.
For patients and researchers interested in gene therapy options for retinal conditions, it would be advisable to consult official clinical trial registries such as ClinicalTrials.gov or contact the developing pharmaceutical company directly for the most current information on OCU410ST development programs.