Lineage Cell Therapeutics announced that restoration of retinal tissue was observed in a patient enrolled in a phase 1/2a study of its lead product candidate, OpRegen, a retinal pigment epithelium (RPE) cell transplant therapy in development for the treatment of dry age-related macular degeneration (AMD). This finding supports the view that dry AMD is not an irreversible, degenerative condition and that some portion of diseased retinal tissue may be recoverable in atrophic end-stage disease patients, according to a company news release.
The loss of retina pigmented epithelium (RPE) cells over time creates progressively larger areas of atrophy in the adult retina, leading to impaired vision or complete blindness, a condition known as dry AMD. Humans lack the innate ability to regenerate retinal tissue and replace lost retina cells, which has led to a presumption that progression of geographic atrophy (GA) may someday be slowed or halted but cannot be reversed. The unique finding from the ongoing OpRegen clinical trial supports a different view, in which an RPE cell transplant can potentially replace or rescue retinal cells in patients who suffer from retinal lesions or degeneration. Lineage reports evidence from a patient with atrophic end-stage disease who received a transplant of allogeneic RPE cells and showed substantial restoration of retinal tissue within the area of GA. Specifically, the area of GA assessed at 9 months was approximately 25% smaller than the patient’s pre-treatment baseline and it grew approximately 50% slower than its historical rate during the subsequent 6 months. These unprecedented findings were initially observed by an independent external advisor using multiple imaging technologies and were subsequently confirmed by the reading center and additional experts in the field of retinal imaging.
“Any therapy which can save photoreceptors and RPE cells in areas of geographic atrophy would be very important to these patients. It is hypothesized that cells in the transition areas at the boundary of the GA are dysfunctional and dying, but not completely lost,” Jordi Monés, MD, PhD, said in the news release. “The addition of new RPE cells may restore the microenvironment in surrounding tissue and contribute to the possibility of restoring function to existing cells that otherwise, if left untreated, would inevitably progress to further expansion of the atrophic region.”
“Our team has independently reviewed these data as part of our ongoing collaborative efforts with Lineage and I think it is evidence of a partially restorative effect in this patient. We have observed apparent RPE regeneration on detailed review of imaging and will look forward to reviewing additional patient data from the OpRegen clinical trial to determine the reproducibility and durability of this unexpected finding,” added Michael Ip, M.D.
“We have evidence at multiple time points which demonstrate a thickening of the outer nuclear layer and restoration of retinal structure. These changes penetrated into the area of GA where those cells are thought to be destroyed and the improvement has persisted over time. The patient also exhibited a consistent 7 to 10 letter improvement in their visual acuity for the past year. These findings are extremely encouraging and it is important that we investigate why this particular individual experienced a restoration of tissue in the boundary areas of their GA,” stated Gary Hogge, Senior Vice President of Clinical and Medical Affairs. “This individual had a multifocal GA and received much greater coverage of cells, either of which may be relevant to these results. Our next steps include seeking to understand the contribution from potentially critical differences in the surgical procedures or baseline characteristics so that we can reproduce this outcome in additional patients.”
“To our knowledge, this is the first time any experimental treatment for dry AMD has demonstrated a reduction, rather than expansion, of an area of atrophy over a clinically meaningful time period. If this finding is confirmed in additional patients, I believe it will create a new paradigm for how we and others approach the treatment of dry AMD and will help advance the incredibly promising area of cell therapy in which we enjoy a leadership position, the directed differentiation and transplant of specific cell types to treat severe diseases and conditions,” stated Brian M. Culley, Lineage CEO.
OpRegen is currently being evaluated in a phase 1/2a clinical study in patients with dry AMD with GA. Seventeen of 21 expected patients have been enrolled to date. The company has observed evidence of benefit in some patients, including increases in best corrected visual acuity (BCVA), reduction in the growth of geographic atrophy, and increases in reading speed. The addition of signs of retinal tissue regeneration provides further support that OpRegen may be a viable treatment for the millions of individuals living with dry AMD, one of the leading causes of vision loss in the world.
OpRegen was originally developed by Drs. Benjamin Reubinoff, MD, PhD, and Eyal Banin, MD, PhD, of Hadassah University and licensed to Lineage’s subsidiary Cell Cure Neurosciences.
Lineage plans to host a live call with two therapeutic area experts Jordi Monés, MD, PhD, Director, Institut de la Màcula and Director, Principal Investigator and Founder, Barcelona Macula Foundation: Research for Vision, and Michael S. Ip, MD, Chief of Vitreoretinal Surgery Service, Doheny Eye Centers, UCLA, on Monday, June 8, 2020 at 4:30 p.m. ET/1:30 p.m. PT. Drs. Monés and Ip will discuss these data and other results of treatment with OpRegen. Interested parties can access the call on the Events and Presentations section of Lineage’s website.