Lineage Cell Therapeutics, Inc. announced the release of exploratory optical coherence tomography (OCT) analysis results on structural changes and visual data from the phase 1/2a study on RG6501 (OpRegen) for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).
Refresh me on RG6501.
RG6501 (OpRegen) is an allogeneic retinal pigment epithelial (RPE) cell therapy derived from human embryonic stem cells and administered as a cell suspension via subretinal injection.
The therapy is in development through an exclusive global collaboration and license agreement between Lineage, Genentech, and Roche.
Now talk about this study.
The phase 1/2a open-label, single-arm, multicenter, dose-escalation trial (NCT02286089) enrolled 24 patients (50+ years of age) with dry AMD in both eyes and funduscopic findings of progressive GA in the macula.
Participants were split into four cohorts based on best-corrected visual acuity (BCVA) (≤ 20/200 [legally blind] in cohorts 1-3; 20/64 to 20/250 in cohort 4) and OpRegen dose, which ranged from the following:
- Cohort 1: ~50,000 cells (n = 3)
- Cohort 2: ~200,000 cells (n = 3)
- Cohort 3: up to ~200,000 cells (n = 6)
- Cohort 4: up to ~200,000 cells (n = 12)
What were the objectives?
Investigators sought to determine the safety and tolerability of OpRegen after the subretinal delivery in varying doses (primary) as well as the potential activity of the therapy by observing visual function and retinal structure changes (secondary).
Findings?
Patients in cohort 4 exhibited outer retinal structure and visual function improvements, with an average 7.6-letter gain in visual acuity (VA) at 12 months; at the same time point, 25% of patients had a ≤ 15-letter gain in VA.
Both outer retinal structure and visual function improvement in the long term for OpRegen-treated eyes continued for up to 4-years in follow up.
What else?
Also in Cohort 4, patients with extensive OpRegen bleb coverage on the atrophic areas and foveal center were noted to have an average of 12.8-letter gain in the treated eye.
In patient cases with extensive coverage, improvements in complete retinal pigment epithelium (RPE) and outer retinal atrophy (cRORA) near the borders of baseline GA were observed.
OCT imaging with segmentation analysis also proved beneficial in determining retinal integrity following OpRegen treatment, with the OCT calculating RPE and external limiting membrane (ELM) loss.
Any adverse effects?
The most frequent ocular adverse events (AEs) reported for all patients were conjunctival hemorrhage/hyperemia (71%) and epiretinal membrane (ERM).
Further, 87% of AEs reported after OpRegen administration were mild.
Overall significance?
The data suggests that OpRegen-treated RPE cells may benefit remaining retinal cells within atrophic areas by counteracting host RPE cell dysfunction / loss.
However, further research is needed on OpRegen to determine the most effective disease stage for intervention and target delivery location.
What’s next?
According to Clinical Trials, the phase 1/2a trial is expected to complete by July 2025.
In the meantime, Lineage is currently enrolling for a phase 2a study (NCT05626114) for OpRegen on a larger scale (n = 60). That study is slated to conclude in September 2029.