Structural Changes Support Gene Therapy's Effect on Geographic Atrophy

Article

New data from imaging analyses on RG6501 were presented at the ARVO 2023 Annual Meeting.

This content originally appeared on our sister site, Ophthalmology Times.

New data from imaging analyses of structural changes and visual data from a phase 1/2a clinical study (NCT02286089) of RG6501 (OpRegen, Lineage Cell Therapeutics) support the therapy's potential to curb disease progression in geographic atrophy associated with dry age-related macular degeneration (AMD).1

These data were presented at the Association for Research in Vision and Ophthalmology (ARVO) 2023 Annual Meeting, held April 23-27, 2023, in New Orleans, Louisiana, by Eyal Banin, MD, PhD, director, Center for Retinal and Macular Degenerations, Department of Ophthalmology, Hadassah-Hebrew University Medical Center, on behalf of Roche and Genentech.

“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 in a statement.2 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.”

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.

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Banine presented data from 12 participants in cohort 4 which demonstrated preliminary evidence of outer retinal structure and visual function improvements with OpRegen. These patients had an average 7.6 letter gain in visual acuity at 12 months in the study eye, and 3 (25%) had a 15 letter or greater gain in visual acuity at 12 months in the study eye. Cohort 4 had up to 4 years of follow-up in which long term vision preservation with outer retinal structure improvement observed in the OpRegen treated eye persisted. 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.1

Findings were also presented on the extent of OpRegen bleb coverage over the area of atrophy, which 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 of RPE and external limiting membrane (ELM) loss were observed in OpRegen treated eyes compared to fellow untreated eyes and 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. Some cases with extensive coverage had resolution of complete RPE and outer retinal atrophy (cRORA) near borders of baseline GA. 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.

Optical coherence tomography imaging, which enables quantitation of changes in RPE and outer retinal structure (such as ELM loss) not possible with fundus autofluorescence imaging following OpRegen subretinal delivery, may be advantageous in assessment of retinal integrity.

“We are extremely pleased to see our 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,” Brian Culley, chief executive officer, Lineage, added to the statement.2

REFERENCES
1. Banin E, Barak A, Boyer D, et al. Exploratory optical coherence tomography (OCT) analysis in patients with geographic atrophy (GA) treated by OpRegen: Results from the Phase 1/2a trial. Presented at: ARVO 2023 Annual Meeting; April 23-27; New Orleans, Louisiana. Presentation 2826
2. RG6501 (OpRegen®) phase 1/2a clinical Results support the potential for OpRegen to slow, stop or reverse disease progression in geographic atrophy secondary to age-related macular degeneration. News release. Lineage Cell Therapeutics. April 26, 2023. https://investor.lineagecell.com/news-releases/news-release-details/rg6501-opregenr-phase-12a-clinical-results-support-potential-0
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