Stem Cell-Engineered Implant for Geographic Atrophy Shows Promise, Long-Term Survival of Cells in Early Trial

A number of companies are developing drug treatments for geographic atrophy, the result of advanced dry age-related macular degeneration (AMD), for which no approved treatments exist. Regenerative Patch Technologies (RPT) is taking a different approach with its stem-cell-based implant, CPCB-RPE1, the subject of recent results from its Phase I/IIa clinical trial.

The implant is designed to act as a tissue-repair technology that replaces the diseased retinal tissue in patients with geographic atrophy (GA), said RPT President Jane Lebkowski, PhD. “The small, specifically bioengineered scaffold is comprised of an ultra-thin parylene membrane that is seeded with a layer of stem cell-derived, retinal pigmented epithelial (RPE) cells,” Dr. Lebkowski explained.

“It mimics the diffusion characteristics of Bruch’s membrane, polarizing the RPE cells when attached to Bruch’s membrane, thereby allowing the cells to function,” she continued. “The cells integrate with photoreceptors and work through Bruch’s membrane to feed into the blood supply.”

Dry AMD is far more prevalent than wet, or neovascular, AMD. The dry form occurs in 90% of AMD patients. GA is the worst form of AMD and is the leading cause of legal blindness in adults, affecting 10% to 20% of people in the US older than age 65.

Phase I/IIa Results
In the study, the worst eye of 15 subjects with GA had the implant safely delivered in an outpatient procedure. Dr. Lebkowski noted that all eyes in the study were legally blind (best-corrected visual acuity [BCVA] ≤ 20/200), and the implant remained in place throughout the trial.

At an average of 34 months post-implantation (range 12 to 48 months), the visual function assessment revealed that 27% (4/15) of eyes had a greater than 5-letter improvement in BCVA and 33% (5/15) remained stable with a BCVA within 5 letters of baseline value. Improvements ranged from 7 to 15 letters, Dr. Lebkowski said. By comparison, the BCVA in the fellow, untreated eye declined by >5 letters (range 8 to 21 letters) in 80% (12/15) of subjects with none experiencing improvement in BCVA.

“The collective data from the Phase I/IIa clinical trial demonstrate the safety and tolerability of the implant along with providing signals of sight-improving activity,” Dr. Lebkowski said. “The data demonstrate that improvement of vision in subjects with GA is attainable and the improvements observed to date are superior to drug therapies currently in late-stage clinical development which only facilitate delay in disease progression.”

Phase IIb Trial On Deck
A planned Phase IIb clinical trial will further evaluate the safety and efficacy of the implant in a larger patient population, Dr. Lebkowski noted. “We are also looking to expand the use of the implant to severe of wet AMD, particularly in Asia where that is the more common form of AMD,” she added.

Eyes from a subject who died more than two years after implantation were examined histologically, revealing the presence of viable, functioning RPE cells associated with the implant in the treated eye. “There is reason to believe that the subretinal space is immune-privileged, so that even with only a short immunosuppression protocol during the peri-implant period, implanted allogeneic RPE cells can survive and function in the retina over the long term,” Dr. Lebkowski said.

Allogeneic cells allow for large-scale manufacturing. RPT has also developed a cryopreserved formulation of the implant for global distribution.

The CPCB-RPE1 implant is placed during a 2 1/2-hour outpatient surgery involving a vitrectomy, following which a cannula dissects the retina from the area of GA. “We have a custom tool that takes up the implant and curls it up like a taco and it puts it into a protective shaft that is delivered through a retinotomy. It ejects very slowly and gently into the subretinal space,” she said.

The Phase I/IIa trial received funding from the California Institute of Regenerative Medicine and Santen Pharmaceuticals. The technology to produce the CPCB-RPE1 implant is exclusively licensed to RPT from the University of Southern California, the California Institute of Technology, and UC Santa Barbara.