Lineage Cell Therapeutics announced that updated interim results from its ongoing, 24-patient phase 1/2a clinical study of its lead product candidate, OpRegen, were reported at the 2021 Association for Research in Vision and Ophthalmology Annual Meeting (ARVO 2021). OpRegen is an investigational cell therapy consisting of allogeneic retinal pigment epithelium (RPE) cells administered to the subretinal space for the treatment of dry age-related macular degeneration (AMD) with geographic atrophy (GA). At ARVO 2021, additional data were presented on 24 patients enrolled in the study, including all 12 patients treated in Cohort 4, which have better baseline vision and smaller areas of GA than earlier cohorts.
“I continue to be very excited about this work and the clinical data generated to date with OpRegen, especially in the better vision Cohort 4 patients,” Principal Investigator Christopher D. Riemann, MD, Vitreoretinal Surgeon and Fellowship Director, Cincinnati Eye Institute and University of Cincinnati School of Medicine, said in a company news release. “There seems to be a significant visual acuity signal in Cohort 4 patients, with most treated eyes having stable or improved vision over time when compared to the contralateral eyes having stable or worsening vision over time. When looking at reading speed progression, treated eyes also seemed to improve while untreated eyes declined. Notably, some individual responders had impressive visual acuity improvements and reductions in GA progression compared to their contralateral eyes. Most importantly, we believe that earlier intervention in less severely affected patients along with a more central placement of transplanted OpRegen cells may increase the likelihood of a clinically beneficial effect. Overall, these results are encouraging and are of a magnitude that could be clinically very important if confirmed in further clinical studies.”
“These new data continue to indicate to us that treatment with OpRegen can generate clinically meaningful outcomes in dry AMD patients with GA, particularly in those with earlier-stage disease,” stated Brian M. Culley, Lineage CEO. “It also appears that earlier intervention in less severely affected patients and more central placement of the transplanted cells may increase the likelihood of observing a benefit. Additionally, among the newly reported data, it was notable that Cohort 4 patients reported improvements in a majority of the vision parameters measured by a validated quality of life questionnaire. The magnitude of these improvements was higher overall in Cohort 4 than in Cohorts 1 through 3, which is consistent with the larger clinical benefit observed among those patients. As this data set matures, our efforts turn next to evaluating the six most recently treated Cohort 4 patients for indications of retinal restoration and reductions in the size and growth of the areas of GA. Our overall objective is to position OpRegen RPE transplants as the clear leader in the race to address the large unmet need in dry AMD with GA and establish Lineage as the pre-eminent allogeneic cell therapy company.”
Updated results presented at ARVO 2021 included a minimum of 4.5 months of follow-up in all 24 patients treated with OpRegen. Nine of twenty-four patients were treated with the “thaw and inject” formulation of OpRegen, two via a standard pars plana vitrectomy (PPV) and seven utilizing the Orbit™ Subretinal Delivery System (Orbit SDS).
Overall, 10/12 (83%) of the Cohort 4 patients’ treated eyes were at or above baseline visual acuity at their last assessment, based on per protocol scheduled visits ranging from 4.5 months to approximately 3 years post-transplant. Improvements in best corrected visual acuity (BCVA) for Cohort 4 patients reached up to +19 letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. In contrast, 10/12 (83%) of the patients’ untreated eyes were below pre-treatment baseline values at the same time points. Among the newly reported data, three (50%) of the more recently treated Cohort 4 patients exhibited marked improvements in BCVA ranging from +7 to +16 letters at their last scheduled assessments of at least 4.5 months. Two additional Cohort 4 patients experienced a gain of 2 letters from their baseline values. One Cohort 4 patient measured 7 letters below baseline. Previously reported structural improvements in the retina, decreases in drusen density, and a trend toward slower GA progression in treated compared to untreated eyes continued. Overall, OpRegen has been well tolerated with no unexpected adverse events or serious adverse events, and evidence of durable engraftment of OpRegen RPE cells have extended to more than 5 years in earliest treated patients, supporting the potential for OpRegen to be a one-time treatment.
A Cohort 4 patient with evidence of retinal restoration and confirmed history of GA growth, which was first reported 9 months following treatment, continues to demonstrate areas of retinal restoration as of their last assessment, approximately 3 years after treatment.
2021 ARVO Presentation OpRegen Data Highlights (As of April 16, 2021):
- In Cohort 1-3 patients (all legally blind at baseline), visual acuity reductions occurred as expected due to progressive GA;
- In Cohort 4 patients, which collectively had smaller areas of GA and higher baseline BCVA as compared to Cohort 1-3 patients, improved or sustained BCVA has been observed in 10/12 (83%) patients as of their last visit prior to this update (range of -7 to +19 letters on the ETDRS chart);
- OpRegen continues to be well-tolerated in all treated patients (N = 24);
- The majority of adverse events were mild (87%);
- Sustained subretinal pigmentation continues to suggest multi-year durability of OpRegen transplants;
- Improved anatomy and function continue to be observed in some patients, including:
- Reduction in drusen;
- Photoreceptor and RPE layer restoration;
- Localized slowing of GA progression in treated areas;
- Better visual acuity via ETDRS scores and reading speed; and
- Improved National Eye Institute Visual Function Questionnaire (VFQ-25) scores.
- Post-treatment surgical interventions occurred in four cases (5 events in 4 patients):
- Three epiretinal membranes (ERM) were surgically peeled. Mild to moderate ERM were observed in an additional 12 out of 17 PPV operated patients. Most ERMs were clinically insignificant.
- Retinal detachment (RD) was observed in 2 out of 17 patients, neither of which appears to be attributable to OpRegen or any study related medications:
- The first case of RD, which occurred in a Cohort 3 patient, was an unsuccessful repair of a post-surgical retinal tear; visual acuity did not regain baseline levels; and
- The second case of RD, which occurred in a Cohort 4 patient, was successfully repaired; post-surgical visual acuity has remained higher than baseline.
- Choroidal neovascularization (CNV) was observed in 3 out of 7 patients receiving OpRegen via the Orbit SDS, all of whom received treatment with an approved anti-VEGF;
- As previously reported, one PPV operated patient developed CNV, which was identified more than two years following treatment.
As part of an ongoing effort to administer the minimally effective dose and duration of immunosuppressive therapy, immunosuppression was utilized only during the perioperative period of approximately 3 months in Cohort 4 patients. One patient received a modified immunosuppressive regimen at baseline, which included no tacrolimus and only mycophenolate mofetil. One patient was diagnosed with COVID-19 shortly after treatment for whom all immunosuppression was halted and reinstated once the patient was asymptomatic. Both patients showed no signs of acute or delayed inflammation or rejection of OpRegen cells with 4.5 months of post-transplant follow up. Other than the reduced regimens described above, immunosuppressants have been discontinued as scheduled, typically within 90 days post-operatively, and no cases of acute or delayed rejection or inflammation due to OpRegen have been reported in any patients treated with OpRegen.
The presentation, “Phase I/IIa Clinical Trial of Transplanted Allogeneic Retinal Pigmented Epithelium (RPE, OpRegen) Cells in Advanced Dry Age-Related Macular Degeneration (AMD): Interim Results” is being featured as part of the Stem Cells/Gene Therapy/Transplantation Session, on May 6, 2021 between 5:15 pm and 6:45 pm EDT by Christopher D. Riemann, MD,(abstract number 3538173).