MONTREAL — A stem cell-derived therapy for advanced geographic atrophy (GA) showed preliminary evidence of vision improvement and retina preservation, according to a small study reported here.
Best corrected visual acuity (BCVA) improved from baseline to 52 weeks with all three dose levels of ASP7317, with the largest improvement with the mid-level dose (9.08 letters). BCVA declined in the fellow eyes of two dosing cohorts and improved in the third but less so than patients who received ASP7317. BCVA had improved at 26 weeks in all three groups, and improvement was maintained during an additional 26 weeks of follow-up, although mean improvement decreased in the low-dose group.
GA area size remained stable, and optical coherence tomography (OCT) detected signs of retinal preservation, including increased retinal pigment epithelium-Bruch’s membrane (RPE-BM) thickness, reported Vivienne S. Hau, MD, PhD, of Kaiser Permanente Bernard J. Tyson School of Medicine in Pasadena, California, at the American Society of Retina Specialists meeting.
“Most retinal treatments aim to slow down the progression of the disease,” Hau said in her introduction to the findings. “What I’m about to talk about is one of the first instances where we can actually repair what has been lost, through human stem cell-derived retinal pigment epithelium therapy.”
“Basically, the study was safe and effective and showed visual improvement and anatomic stabilization,” she added. “The patient questionnaire showed that vision was generally stabilized or improved. [The study] encourages us for ongoing studies.”
Session co-moderator Sunir Garg, MD, of Wills Eye Hospital in Philadelphia, asked about patient selection for the therapy.
“If I understood correctly, you saw more effect closer to where the cells were placed, and in the original phase I trial, it was a pretty broad lesion area, like 30 mm2,” said Garg. “Do you think, because of that finding, that this technology will be best for patients with certain lesion sizes, so you can get that effect? Do we get to the point where the lesion is too big, and the cells just end up being too far away to exert more global effect?”
Hau said more research is needed to determine whether an optimal injection site or lesion area size exists. The first cohort treated had severe vision loss, which was associated with “a very large lesion size.”
“I suspect with future phases, we may look at lesion sizes that may be smaller, and maybe we will see if there is a continuation of the observation you made,” she said.
ASP7317 is an RPE cell therapy derived from human embryonic stem cells, delivered by subretinal injection. Researchers hypothesize that the therapy can restore photoreceptor function and improve vision.
The treatment was evaluated in a phase Ib trial involving nine patients with GA and severe vision impairment (17-37 letters) in three dose-defined cohorts. Following vitrectomy, each patient received a single subretinal injection of ASP7317. The primary endpoint was safety. Secondary and exploratory endpoints included change in BCVA, GA lesion growth rate, and Patient Global Impression of Change (PGIC) scale scores.
The treatment was generally well tolerated with no unexpected adverse events (AEs), and procedure-related events were consistent with those associated with vitrectomy, said Hau. No graft failure occurred, and no patients had persistently elevated intraocular pressure or developed tumors. The most common ocular AE was conjunctival hemorrhage (five patients), and diarrhea was the most common systemic AE (three patients).
After 26 weeks of follow-up, mean BCVA had improved by 4.25 to 10.50 letters across the three cohorts, and untreated fellow eyes had BCVA loss of 4.0 and 5.65 letters in two cohorts and a gain of 2.56 letters in the high-dose cohort. At 52 weeks, mean BCVA improvement was 5.50 letters in the low-dose cohort and 9.08 letters in the mid-level cohort, compared with declines of 2.5 and 5.75 letters in untreated eyes in the same cohorts. Follow-up to 52 weeks is ongoing in the high-dose cohort.
Focusing on the two dose levels selected for further evaluation, Hau said mean GA lesion size at 52 weeks in the mid-dose cohort was 0.06 mm in treated eyes as compared with 0.25 mm in untreated eyes. The 26-week results for the high-dose cohort showed an increase of 0.07 mm in treated eyes and 0.12 mm in untreated eyes.
For the subgroup of patients who gained 10 or more letters in BCVA, OCT analysis showed stabilization of GA area and ellipsoid zone (EZ)-RPE atrophy along with improved RPE-BM thickness. In fellow eyes with 10-letter loss of BCVA, GA lesion size, EZ-RPE atrophy, and RPE-BM thickness all increased.
PGIC results from week 8 through week 26 showed that a majority of patients reported improved vision (much, moderate, a little), and no patients reported worsening. Incomplete data for week 52 showed that two patients reported improved vision, one saw no change, and one perceived BCVA to be a little worse.
