ARVO 2023: RG6501 (OpRegen) Phase 1/2a clinical results support the potential for cell therapy to curb disease progression in geographic atrophy

In data presented at ARVO 2023 in New Orleans, it was noted OCT imaging with segmentation analysis is advantageous in the assessment of retinal integrity post-treatment. (Image courtes of Adobe Stock)

Lineage Cell Therapeutics Inc. today announced that results from imaging analyses of structural changes and visual data from a Phase 1/2a clinical study of RG6501 (OpRegen) were presented at the Association for Research in Vision and Ophthalmology annual meeting in New Orleans.

The presentation, “Exploratory optical coherence tomography (OCT) analysis in patients with geographic atrophy (GA) treated by OpRegen: Results from the Phase 1/2a trial” was presented by Eyal Banin, MD, PhD, director of the Center for Retinal and Macular Degenerations, Department of Ophthalmology at Hadassah-Hebrew University Medical Center, on behalf of Roche and Genentech.

According to the company, RG6501 is an allogeneic retinal pigment epithelial (RPE) cell therapy currently in development for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). It is being developed under an exclusive global collaboration between Lineage, Roche and Genentech, and is currently being evaluated in a Phase 2a clinical study (NCT05626114) in patients with GA secondary to AMD.

Brian Culley, CEO of Lineage, pointed out the company was pleased to see its observations of improved retinal structure in the initial clinical study of OpRegen are being reinforced by additional external and independent analyses of the images performed by Genentech and Roche.

“Looking ahead, we are excited to collaborate with Genentech and Roche on the ongoing Phase 2a study of OpRegen, which is currently enrolling patients and open at multiple sites in the US, with more sites expected to come online this year,” Culley said.

“I have been closely involved with the OpRegen program since its beginning and I continue to be excited about the potential therapeutic benefit for patients afflicted with dry AMD and geographic atrophy, a progressive and debilitating disease that significantly affects the quality of life of many,” Banin said. “These data further highlight the potential for a single dose of OpRegen to provide significant clinical outcomes for patients in a disease with a tremendous unmet need.”

ARVO presentation highlights

• Preliminary evidence of outer retinal structure and visual function improvements with OpRegen was observed in patients with GA and impaired vision (Cohort 4 [n=12]):
• Patients in Cohort 4 had an average 7.6 letter gain in visual acuity at 12 months in the study eye;
• Three patients in Cohort 4 (25%) had a 15 letter or greater gain in visual acuity at 12 months in the study eye.
• Long term vision preservation with outer retinal structure improvement observed in the OpRegen treated eye persisted for up to 4 years of follow-up.
• The extent of OpRegen bleb coverage over the area of atrophy may be important to optimize patient outcomes:
• In patients with extensive OpRegen bleb coverage, maintenance or improvement of outer retina structure was observed in treated eyes compared to worsening in fellow eyes:
• Five patients in Cohort 4 who had a surgically delivered bleb containing OpRegen that extensively covered their atrophic areas and the foveal center, experienced an average 12.8 letter gain in their study eye.
• Improvement in outer retinal layers also correlated with the extent of OpRegen bleb coverage:
• Slower rates ofRPE and external limiting membrane (ELM) loss were observed in OpRegen treated eyes compared to fellow untreated eyes;
• Patients with extensive OpRegen bleb coverage of the atrophic area had maintenance or improvement of RPE and ELM layers compared to patients with limited OpRegen bleb coverage.
• Resolution of complete RPE and outer retinal atrophy (cRORA) near borders of baseline GA were observed in cases with extensive coverage:
• Signs of improvement in areas of cRORA included: greater hyperreflectivity at the level of RPE/ Bruch's membrane (BM); less choroidal hypertransmission; reduction of retinal subsidence, and greater continuity of outer retinal layers.
• OCT imaging with segmentation analysis may be advantageous in assessment of retinal integrity following OpRegen treatment:
• OCT enables quantitation of changes in RPE and outer retinal structure (such as ELM loss) not possible with FAF imaging following OpRegen subretinal delivery.
• One patient in Cohort 4 maintained improvement in visual acuity at 4 years post-treatment in the study eye (+3 letters read), compared to losing 30 letters in the untreated eye.
• Overall, these data suggest that OpRegen RPE cells may provide support to the remaining retinal cells within atrophic areas by counteracting host RPE cell dysfunction and loss.
• Further assessment of the optimal disease stage for intervention and target delivery location of OpRegen in a larger clinical study is needed to confirm these preliminary findings.
• A Phase 2a study evaluating the success of OpRegen delivery to target areas of GA is currently enrolling patients.