Retinal Tissue Restored in Patients with Dry AMD, Heralding Paradigm Shift
Retinal tissue has been regrown in three patients with age-related macular degeneration (AMD) with geographic atrophy or dry (atrophic) AMD in a Phase I/IIa study conducted by Lineage Cell Therapeutics.
“This has the potential to offer a whole new paradigm to treat the disease,” Brian Culley, CEO of Lineage, told BioSpace.
Adding to the original findings reported last year, two additional patients treated in November demonstrated a reduction in atrophied retinal tissue, making them – to the company’s knowledge – the only patients with dry AMD to actually regrow retinal tissue and improve visual acuity.
The treatment, OpRegen®, is an allogeneic retinal pigment epithelium (RPE) cell transplant therapy. In a 12-person study of dry AMD patients who retained some vision, 83% reported the vision in the treated eye was at or above baseline. Coincidentally, the same percentage reported that vision in their untreated eye worsened. So, although OpRegen® doesn’t reverse blindness, by causing tissue to regrow, it may be able to prevent people with dry AMD from worsening and eventually becoming blind.
In the study, RPE atrophy was measured using clinical high-resolution optical coherence tomography (OCT). It showed new areas of RPE monolayer with overlying ellipsoid zone, external limiting membrane, and outer nuclear layer that were not present during the baseline assessment. Visual acuity likewise increased.
These findings suggest the new RPE cells integrated with functional photoreceptors in areas that previously lacked those cells. The effects were most prominent in the transitional area around the primary area of geographic atrophy. Taken all together, they support the notion that atrophic AMD is reversible and that some portion of the diseased retinal tissue can be recovered.
OpRegen® is composed of functional retinal pigment epithelia (RPE) cells that Lineage manufactures by the billions from a single cell line and transplants into the eye via pars plana vitrectomy as part of a 30-minute surgery using local anesthesia.
“When we place the cells in the subretinal space, they clear the waste material and support the surrounding tissues. There also may be some degree of trophic, or nourishing, effect on nearby cells,” Culley said.
The therapy was administered as a one-time treatment and cells have persisted in the earliest-treated patients for more than five years.
Lineage plans to follow the patients for six months and then design another clinical study with input from the FDA to enable a regulatory filing market authorization.
“We believe the next trial could be a registrational study,” he said.
“Dry AMD is a progressive degenerative condition. It’s a one-way street,” Culley said. “Dry AMD cannot be reversed and has no FDA-approved treatments.”
There are a few efforts to prevent the area of atrophy from expanding, but no therapies – save OpRegen – have shown the ability to reverse the damage. Lineage Cell Therapy’s data is early, he admitted, but reiterated that the therapy appears to be capable of reversing the damage.
“Human beings cannot regrow retinal tissue, so we believe our transplanted RPE cells are responsible for these positive changes”, Culley said.
The improvements in vision are not just significant for surgeons, but are also meaningful to patients. Importantly, the benefits observed in the retinal restoration patients have been maintained for as long as three years – the duration (so far) of the longest available follow-up.
“That’s not what normally happens in dry AMD,” Culley said. Because the disease is progressive and degenerative, “A treatment that even could stabilize the disease would be a tremendous success,” so a therapy that reverses the disease could be life-changing.
Life-changing” is, in fact what one of the patients called it. “She called her physician, literally crying for joy,” Culley said, recounting a conversation with one of the principal investigators. “He said he’s never had that happen with patients who had dry AMD.”
This therapy is based on a long-hypothesized idea “that in atrophic AMD patients, cells in the transition areas at the boundaries of the geographic atrophy are dysfunctional and dying, but not completely lost Jordi Monés, M.D., Ph.D., director, Institut de la Màcula, and director, principal investigator and founder, Barcelona Macula Foundation, said in an earlier statement.
Now, Monés continued, “These unprecedented findings provide further evidence that the addition of new RPE cells may restore the microenvironment of the surrounding tissue and contribute to the survival and function of existing cells that otherwise, if left untreated, would inevitably progress to further expansion of the atrophic region.”
Lineage is patenting the technology internationally under the Patent Cooperation Treaty, which enables a company to seek patent protection in the 150-PCT signatory countries by filing one patent application. By filing under the PCT, the allowed claims of national patents based on the PCT application would have an estimated expiration date no earlier than May 24, 2041, which is somewhat longer than those filed one country at a time.
“The production methods that create our cells cannot be replicated by competitors, but it’s prudent to take a belt and suspenders approach and also protect our materials and manufacturing methods with traditional patents,” Culley said.