36-Month Results from Phase 1/2a Clinical Study of RG6501 Released

Lineage Cell Therapeutics has announced 36-month results from its phase 1/2a clinical study (NCT02286089) of RG6501 (OpRegen), developed for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

Long-Term Data Presented at CTS 2025

On behalf of Roche and Genentech, Christopher D. Riemann, MD, vitreoretinal surgeon and fellowship director at Cincinnati Eye Institute and the University of Cincinnati School of Medicine, shared these findings at Clinical Trials at the Summit (CTS) 2025. His presentation, titled “OpRegen Retinal Pigment Epithelium (RPE) Cell Therapy for Patients with Geographic Atrophy (GA): Month 30 Results from the Phase 1/2a Trial,” highlighted the durability of treatment outcomes.

About RG6501 (OpRegen)

RG6501 is described as “a suspension of human allogeneic retinal pigment epithelial (RPE) cells,” administered via subretinal delivery. This approach aims to support retinal health and improve both retinal structure and function by counteracting RPE cell loss within GA lesions.

Brian M. Culley, CEO of Lineage, noted,

“Long term clinical outcomes following a single administration of OpRegen cell therapy is challenging the long-held view that GA causes irreversible damage. A key finding from the Lineage-run phase 1/2a trial was the importance of extensive placement of cells around the area of atrophy. Among patients who received fulsome coverage by OpRegen cell therapy, anatomical and functional benefits from a single administration have lasted at least 3 years.”

He added that treated eyes showed mean BCVA scores above baseline at 12, 24, and 36 months, demonstrating both consistency and durability.

Study Design and Patient Cohorts

This phase 1/2a study is an open-label, single-arm, multi-center, dose-escalation trial evaluating a single subretinal administration of OpRegen in patients with bilateral GA secondary to AMD. A total of 24 patients were enrolled across four cohorts:

       • The first three cohorts enrolled only legally blind patients with BCVA of 20/200 or worse.

       • Cohort 4 enrolled 12 patients with BCVA ranging from 20/65 to 20/250 and smaller mean areas of GA.

Additionally, Cohort 4 patients received a new “thaw-and-inject” formulation of RG6501, which can be shipped directly to sites and used immediately after thawing, eliminating the need for a separate dose preparation facility.

Study Objectives

The primary objective was to evaluate the safety and tolerability of RG6501, focusing on the incidence and frequency of treatment-emergent adverse events. Secondary objectives assessed preliminary activity by measuring changes in various ophthalmic parameters.

Key Findings from CTS 2025

       • Patients in Cohort 4, who had less advanced GA, demonstrated improvements in visual acuity at 12 months (primary endpoint), sustained through 24 and 36 months.

       • Gains in BCVA measured at month 12 remained evident through month 36 in Cohort 4.

       • Mean change in BCVA for patients (n=10) completing 3-year follow-up was +6.2 ETDRS letters at 36 months, compared to +5.5 letters at 24 months.

       • Patients with extensive RG6501 coverage of GA areas showed greater BCVA and outer retinal structure improvements, persisting through month 36.

                   • Specifically, five patients with extensive coverage saw mean BCVA gains of +9.0 ETDRS letters at 36 months, compared to +7.4 at 24 months.

Sustained Structural Improvements on OCT

       • Quantitative OCT analysis showed sustained improvements in retinal structure in treated eyes through 36 months.

       • In the subgroup of five patients with extensive bleb coverage:

                 • Mean improvement in RPEDC area was maintained from +2.6 mm² at 24 months to +1.0 mm² at 36 months.

                 • Mean ELM area gains were +0.8 mm² at 24 months and +0.3 mm² at 36 months.

       • In contrast, untreated fellow eyes showed declines in RPEDC area (-2.8 mm² at 24 months, -3.8 mm² at 36 months) and ELM area (-1.9 mm² at 24 months, -3.4 mm² at 36 months).

Culley summarized,

“In short, patients who received significant coverage of OpRegen cell therapy across their GA are exhibiting long-term outcomes consistent with meaningful disease stabilization and even improvement. We are excited to see any additional insights which our partners, Roche and Genentech, may uncover from the ongoing GAlette study.”

Next Steps: GAlette Phase 2a Study

The phase 2a GAlette study (NCT05626114), which aims to evaluate the success of subretinal delivery of OpRegen cell therapy to target areas of GA, is currently enrolling patients.