OpRegen Continues to Show Promise in Updated Dry AMD Data

Jordi Monés, MD, PhD

OpRegen, which consists of allogeneic retinal pigment epithelial (RPE) cells, led to restoration of retinal tissue for 3 out of 4 patients (75%) with dry age-related macular degeneration (AMD) and geographic atrophy (GA) who received the treatment across a wide area of atrophy, according to Lineage Cell Therapeutics, the company developing the therapy.

These new findings build on data presented in early May at the 2021 ARVO annual meeting from cohort 4 of a phase 1/2 study. The study enrolled 12 patients in cohort 4 of the study, all with dry AMD and best correct visual acuity (BCVA) of 20/64 to 20/250. Cohorts 1-3 of the study also included 12 patients with BCVA of 20/200 who were considered legally blind.

In the ARVO data, 83% of patients had stable or improved BCVA following treatment with the cell therapy this was compared with a decline in visual acuity in 83% of untreated eyes. One patient had signs of retinal restoration at month 9, which persisted through month 36 at the ARVO assessment. The additional 2 patients with restoration were from a group of 3 patients who were treated in November 2020 in the study. In these procedures, the surgeons were able to cover most of the atrophy with OpRegen cells.

“After reporting the first case of retinal restoration last year, it is extremely exciting for me to see retinal restoration replicated in additional OpRegen-treated patients,” Jordi Monés, MD, PhD, director, Institut de la Màcula and director, principal investigator and founder, Barcelona Macula Foundation, said in a statement. “Confirmation of restoration was performed by independent experts using multimodality imaging techniques and these new cases reinforce earlier findings that treatment with OpRegen can save dysfunctional photoreceptors and replace RPE cells in areas of geographic atrophy, which could provide a remarkable treatment opportunity for this patient population.”

The OpRegen treatment consists of RPE cells that have been derived from undifferentiated human embryonic stem cells. The RPE cells do not undergo any genetic alterations and are either cryopreserved to be thawed prior to treatment (thaw and treat [TAI]) or suspended in an ophthalmic balanced salt solution for administration.

In cohort 4 of the study, patients received OpRegen by pars plans vitrectomy (PPV) and retinotomy (n = 5) or by the Orbit subretinal delivery system (n = 7). The mean age in the PPV arm was 78.1 years and was 74.2 years in the Orbit group. The baseline ETDRS BCVA was 49.6 letters in the PPV group and was 41.4 in the Orbit group. The mean GA area was 6.2 mm² and 8.2 mm² and the mean follow-up was 711 days and 361 days, for PPV and Orbit, respectively. The TAI formulation was used for all 7 Orbit-treated patients and for 2 of the PPV-treated patients.

For the retinal improvements, there were improvements in imaging on optical coherence tomography (OCT) at the assessment compared with baseline. On high resolution OCT, new areas of RPE monolayer with overlying ellipsoid zone were seen in all 3 of the patients. Moreover, new external limiting membrane and outer nuclear layers were observed, which were not present at the time of baseline assessment. In addition to improvements in retinal tissue, lineage noted that the 3 patients also experienced increases in visual acuity within 6 months of the treatment.

“It has long been hypothesized that in atrophic AMD patients, cells in the transition areas at the boundaries of the GA are dysfunctional and dying, but not completely lost,” said Monés. “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.”

For the 2 patients, additional signs of efficacy with OpRegen were noted in the area surrounding the GA application site. The company noted signs of complete resolution of incomplete RPE and outer retinal atrophy lesions following OpRegen transplant. Moreover, areas with complete RPE and outer retinal atrophy had full-thickness restoration.

“To our knowledge, these 3 patients represent the only examples of an experimental treatment for dry AMD demonstrating a reduction, rather than attenuating further expansion, of an area of atrophy in humans,” Brian M. Culley, Lineage CEO, said in a statement. “Now that these findings of retinal restoration have been confirmed in multiple patients over clinically meaningful time periods, we believe we are in a position to pioneer a new paradigm for how we and others evaluate and treat atrophic AMD.”

Overall, according to ARVO data, there were no cases of acute or delayed inflammation with the RPE therapy. Moreover, there were no sustained increases in intraocular pressure. All patients in the study reported at least 1 adverse event, with the majority being mild in severity (87%). More adverse events were reported in PPV-treated patients (n = 136) compared with Orbit-treated group (n = 29).

To assess quality of life, the investigators also conducted the National Eye Institute Visual Function Questionnaire (VFQ-25) for patients in cohort 4. Overall, there was improvement noted in 9 of the 11 categories across 5 patients screened. Overall, 100% of patients noted improvements in near activities and mental health and 80% reported improvements in general vision and role difficulties along with other measures.

“Importantly, in addition to thickening of the outer nuclear layers and restoration of retinal structures in these patients, we also have observed durable improvements in visual acuity,” said Culley. “Additional evidence collected recently supports our belief that treatment with OpRegen can provide patients not only with improvements in the anatomy and the structure of their retina and visual acuity, but also enhance quality of life.”

Lineage plans to discuss the findings from the additional 2 patients with its board of scientific advisors, to determine if any clinical development changes will be necessary. Moreover, the company is exploring potential paths toward regulatory submission for the cell therapy. Based on prior findings, OpRegen previously received a fast track designation from the FDA.