Results from a Phase 1/2a clinical study of RG6501 (OpRegen) show rapid improvement in outer retinal structure in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD), according to data presented at the 2023 EURETINA Congress.
The findings, presented by Dr. Adiel Barak, Professor of Ophthalmology and Vitreoretinal Unit Director at Tel Aviv Medical Center, demonstrated that all five patients in cohort 4 who received extensive coverage of their GA lesions with RG6501 showed structural improvements within the first three months after treatment.
RG6501, developed by Lineage Cell Therapeutics in collaboration with Roche and Genentech, is a suspension of human allogeneic retinal pigmented epithelial (RPE) cells designed to counteract RPE cell loss in areas affected by GA.
Rapid Structural Improvements
The most striking finding from the study was the speed at which improvements were observed. Among the five patients in cohort 4:
- One patient showed improvement as early as day 1 post-treatment
- One patient showed improvement by day 14
- Two patients showed improvement by month 1
- One patient showed improvement by month 3
"These data suggest that OpRegen RPE cells may provide direct support to the patients' remaining retinal cells within atrophic areas, and that the improvements to retinal structure can be detected within the first three months following a single administration," said Brian Culley, CEO of Lineage Cell Therapeutics.
Visual Acuity Gains
Beyond structural improvements, the treatment also yielded meaningful visual acuity benefits. The five patients in cohort 4 experienced:
- An average 4.4 letter best-corrected visual acuity (BCVA) gain by 3 months
- An average 12.8 letter BCVA gain by 1 year compared to baseline
These gains are particularly significant given that GA typically results in progressive, irreversible vision loss.
Assessment Methodology
The study employed rigorous evaluation methods to confirm structural improvements. Optical coherence tomography (OCT) images were reviewed by three independent graders who assessed changes from the day after surgery through subsequent follow-up visits.
Structural improvement was qualitatively defined as meeting all of the following pre-specified criteria:
- Reduction in outer plexiform layer (OPL) and/or inner nuclear layer (INL) subsidence
- Reappearance of external limiting membrane (ELM)
- Increased hyperreflectivity and/or thickness of RPE and/or Bruch's membrane, or reduction of hypertransmission on at least two non-adjacent B scans
Durability of Response
The durability of the treatment effect appears promising. The patient who demonstrated improvement on day 1 exhibited persistence of structural improvement as measured by OCT, with resolution of areas of complete RPE and outer retinal atrophy (cRORA) features at 24 months following treatment.
Researchers are still evaluating the durability of retinal structure improvements beyond the 12-month primary endpoint in other patients.
Mechanism of Action
The study results suggest that RG6501's mechanism of action involves the delivered RPE cells providing support to the remaining retinal cells within atrophic areas. Importantly, structural improvement was only observed within GA lesions with extensive coverage with the surgical bleb containing RG6501 in suspension.
Ongoing Development
RG6501 is currently being examined in a Phase 2a clinical trial (NCT 05626114) in patients with GA secondary to AMD, which is still enrolling patients. The therapy represents a novel approach to treating GA, for which treatment options have historically been limited.
"We look forward to additional, future clinical data updates on the OpRegen program from our partners, Roche and Genentech," added Culley, highlighting the ongoing development efforts for this promising therapy.
The positive early results from this study provide hope for patients with GA, a condition that affects millions worldwide and is a leading cause of blindness in older adults.
