36-month results from phase 1/2a clinical study of RG6501 released

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

On behalf of Roche and Genentech, Christopher D. Riemann, MD, Vitreoretinal Surgeon and Fellowship Director, Cincinnati Eye Institue and University of Cincinnati School of Medicine, presented the data at the Clinical Trials at the Summit (CTS) 2025 in a presentation titled, “OpRegen Retinal Pigment Epithelium (REP) Cell Therapy for Patients with Geographic Atrophy (GA): Month 30 Results from the Phase 1/2a Trial.”

RG6501 is “a suspension of human allogeneic retinal pigment epithelial (RPE) cells” in development for the treatment of GA, a press release said. Through subretinal delivery, the cell therapy has the potential to support retinal cell health and improve retinal structure and function, counteracting RPE cell loss in GA lesions.

“Long term clinical outcomes following a single administration of OpRegen cell therapy is challenging the long-held view that GA causes irreversible damage,” said Brian M. Culley, Lineage CEO, in a press release. “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 continued, “Importantly, OpRegen-treated eyes have exhibited mean BCVA scores above baseline at each of the 12-, 24-, and m36-month timepoints, demonstrating consistency as well as durability.”

The phase 1/2a study is an open-label, single-arm, multi-center, dose-escalation trial evaluating a single administration of OpRegen cell therapy delivered subretinally in patients with bilateral GA secondary to AMD.1

There were 24 patients enrolled across 4 cohorts. The first 3 cohorts enrolled only legally blind patients with best corrected visual acuity (BCVA) of 20/200 or worse. Cohort 4 enrolled 12 patients with impaired vision of BCVA from 20/65 to 20/250 with smaller mean areas of GA. Additionally, Cohort 4 included patients treated with a new “thaw-and-inject” formulation of RG6501 cell therapy, according to a press release. This formulation can be shipped directly to sites and used immediately upon thawing, which removes the complications and logistics of having to use a dose preparation facility, a press release said.

Evaluating the safety and tolerability of RG6501 cell therapy, as addressed by the incidence and frequency of treatment-emergent adverse events, was the primary objective of the phase 1/2a study. Secondary objectives included evaluating the preliminary activity of RG6501 cell therapy treatment by addressing the changes in ophthalmic parameters measured by various methods of primary clinical relevance.1

Key takeaways from the CTS 2025 presentation¹

• Patients in Cohort 4, who had less advanced GA compared to other cohorts, saw improvement in visual acuity present at 12 months (primary endpoint), 24 months, as well as 36 months.
• Following subretinal administration of RG6501, gains in best corrected visual acuity (BCVA) measured at month 12 remain evident through month 36 in Cohort 4 patients.
• Mean change in BCVA among treated eyes for patients (n=10) completing 3-year follow up was +6.2 letters compared to +5.5 letters at 24 months. This was measured based on the Early Treatment Diabetic Retinopathy Study (ETDRS) assessment.
• In patients with extensive RG6501 bleb coverage of their GA area, improvement in BCVA and outer retinal structure was greater than in patients with limited coverage and persisted through month 36.
• Effects were greater on average in the 5 patients with extensive RG6501 cell therapy coverage of atrophic areas at the time of surgical delivery. These patients saw mean change of +9.0 ETDRS letters in BCVA for those completing 3-year follow-up, compared to +7.4 ETDRS letters at 24 months.
• Through quantitative optical coherence tomography (OCT) analysis, sustained evidence of retinal structural improvement through 36 months was observed in treated eyes of Cohort 4 patients following a single subretinal administration of RG6501 cell therapy.
• At month 36, sustained evidence of retinal structure improvements in external limiting membrane (ELM) and RPE drusen complex (RPEDC) layers on OCT was observed in the subgroups of 5 patients in Cohort 4 with extensive RG6501 cell therapy bleb coverage of atrophic areas at the time of surgical delivery.
  • Mean improvement of RPEDC area compared with baseline was maintained in treated eyes for 24 months (+2.6 mm²) to 36 months (+1.0 mm²).
    • In comparison, mean change in RPEDC area decreased in untreated fellow eyes from 24 months (-2.8 mm²) to 36 months (-3.8 mm²).
  • Mean change in ELM area was maintained in treated eyes for 24 months (+0.8 mm²) to 36 months (+0.3 mm²).
    • In comparison, mean change in ELM area decreased in untreated fellow eyes for 24 months (-1.9 mm²) to 36 months (-3.4 mm²).

“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,” Culley said in the release. “We are excited to see any additional insights which our partners, Roche and Genentech, may uncover from the ongoing GAlette study, which is investigating the best way to deliver OpRegen cell therapy to patients with GA secondary to age-related macular degeneration (AMD).

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

Reference:

1. OpRegen® (RG6501) 36-Month Visual Acuity Results Featured at Clinical Trials at the Summit 2025. BioSpace. Published June 23, 2025. Accessed June 24, 2025. https://www.biospace.com/press-releases/opregen-rg6501-36-month-visual-acuity-results-featured-at-clinical-trials-at-the-summit-2025

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