Lineage, Pioneering a New Branch of Medicine — OpRegen Continues to Show Promising Results in Dry AMD with Geographic Atrophy

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Cheri's Story | OpRegen for Dry AMD | Lineage Cell Therapeutics

Lineage Cell Therapeutics Inc. LCTX LCTX recently provided an update on its lead program OpRegen®, a cell replacement therapy for dry age-related macular degeneration (AMD) with geographic atrophy (GA). 

Lineage is pioneering a new branch of medicine, which is manufacturing differentiated cell types and transplanting those cells into the body, to restore or improve function which has been lost due to injury or disease. 

The data from an ongoing Phase 1/2a clinical study continued to demonstrate that a single administration of OpRegen, an investigational cell therapy consisting of allogeneic retinal pigment epithelium (RPE) cells administered to the subretinal space, can provide both anatomical and functional improvements in patients with dry AMD with GA.

“We now have evidence that our cell transplant approach with OpRegen may be able not only to slow the dry AMD disease process but even to halt or reverse it. We are seeing improvements to visual acuity in the majority of treated eyes and we believe OpRegen, which currently is contemplated as a one-time treatment, may have an enormous advantage in terms of compliance and convenience over traditional drugs being developed by competitors that require monthly or semi-monthly injections,” Brian M. Culley, Chief Executive Officer told Benzinga.

“Notably, OpRegen is the only investigational therapy that has shown evidence of retinal restoration in atrophic dry AMD patients. While competing efforts are focused on reducing the growth rate of geographic atrophy, Lineage has reported multiple patients whose areas of atrophy have stabilized or reduced in size for as long as three years. All other approaches in clinical development are directed toward slowing the expansion of the area of atrophy and cannot reverse it.” 

“The durability of the improvements to vision, when coupled with the clear structural improvements seen in patients who received thorough coverage of OpRegen across their areas of atrophy, strongly suggest that cell therapy may be able to achieve therapeutic benefits that are beyond the reach of targeted drugs or antibodies. We are extremely pleased that our data has moved in a positive direction with each interim update we have provided,” Mr. Culley added.

Highlights from recent OpRegen data updates include:

• The first reported case of retinal tissue restoration showed zero growth of atrophy at 33 months
• The second case of retinal tissue restoration showed a 10% reduction in atrophy at 8 Months
• Statistically significant evidence of a treatment effect observed in cohort 4 patients
• 67% of better vision cohort 4 patients at or above baseline visual acuity

A Disease with No Approved Treatments 

Age-related macular degeneration (AMD) is an eye disease that can blur the sharp, central vision in patients and is the leading cause of vision loss in people over the age of 60. There are two forms of AMD: dry (atrophic) AMD and wet (neovascular) AMD. Dry (atrophic) AMD is the more common of the two forms, accounting for approximately 85-90% of all cases. There are currently no U.S. Food and Drug Administration (FDA), or European Medicines Agency, approved treatment options available for patients with atrophic AMD.

When the macula — the small central portion of the retina — wears down, the light-sensing nerve tissue at the back of the eye begins to deteriorate. This retinal pigment epithelium (RPE) is a monolayer of pigmented cells, and when these cells cease to function, they begin to die off. As a result, patients experience the degeneration of photoreceptors in the eyes, and dry AMD starts to take over.  

As it evolves into geographic atrophy (GA), or advanced dry (atrophic) AMD, patients experience significant vision loss. The loss of RPE cells over time creates progressively more prominent areas of atrophy in the adult retina. The decline leads to impaired vision or complete blindness. 

Humans lack the ability to regenerate retinal tissue and replace lost retina cells on their own, leading to the presumption that GA progression could be slowed or halted but never be reversed. 

Lineage’s approach to treating dry AMD is to transplant healthy new retina cells that replace or support the ones that have died off or are dysfunctional. The company believes that replacing the entire cell avoids risks and limitations inherent in approaches that may target just a single pathway or approaches that target a certain mutation, which might only be relevant to a small subset of patients.

The Results in a Nutshell

Lineage is currently evaluating OpRegen in an ongoing Phase 1/2a clinical study, which enrolled 24 patients across 4 different cohorts with varying stages of vision loss. The most updated results include a minimum of 9 months of follow-up in all 12 patients treated in Cohort 4, which as a group had better baseline vision and smaller areas of GA at baseline than earlier cohorts. 

Three cohort 4 patients with evidence of retinal restoration and confirmed history of GA growth have continued to demonstrate areas of retinal restoration. The first of these patients demonstrated a reduction in their area of atrophy for multiple years and had still reflected zero growth through 33 months following treatment with OpRegen. The second patient with evidence of restoration of critical retinal structures showed a 10% reduction at approximately 8 months after treatment. Despite areas of atrophy expanding slowly, evidence of retinal restoration appeared as early as two to three months after treatment.

Overall, 67% of the Cohort 4 patients’ treated eyes were at or above baseline visual acuity at their last assessment, ranging from 9 months to over 3 years post-transplant. Conversely, 75% of the patients’ untreated eyes were below baseline visual acuity. Comparing all treated eyes to all fellow (untreated) eyes showed an average difference of 10.8 letters read in Cohort 4 patients at their last assessment. Across the study, in patients with previously reported structural improvements in the retina, decreases in drusen density, and a trend toward slower GA progression in treated compared to untreated eyes have continued to be present. Evidence of durable engraftment of OpRegen RPE cells has extended to more than 5 years in the earliest treated patients. 

The unique findings from the ongoing OpRegen clinical study support the view that an RPE cell transplant can potentially replace or support retinal cells in patients who suffer from retinal lesions or degeneration. The totality of these findings supports the view that atrophic AMD is not an irreversible, degenerative condition and that some portion of diseased retinal tissue may be recoverable.

Recent updates from the Phase 1/2a study can be found here and here.  

Lineage anticipates another clinical update at the 2021 Annual Academy of Ophthalmology Annual Meeting, the largest ophthalmology meeting in the world which takes place in New Orleans, November 12 - 15, 2021.

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The preceding post was written and/or published as a collaboration between Benzinga’s in-house sponsored content team and a financial partner of Benzinga. Although the piece is not and should not be construed as editorial content, the sponsored content team works to ensure that any and all information contained within is true and accurate to the best of their knowledge and research. This content is for informational purposes only and not intended to be investing advice.