OpRegen® is retinal pigment epithelium cell replacement therapy that is currently in a Phase I/IIa, multicenter clinical trial for the treatment of advanced dry-age-related macular degeneration (“dry-AMD”) with geographic atrophy. Age-related macular degeneration, also known as “AMD”, is a common eye disorder causing impaired central vision in which loss of retinal pigment endothelium (RPE) cells impairs drusen clearance and facilitates macular degeneration. Using a proprietary directed differentiation method, OpRegen® is a formulation of animal-free RPE cells with high yield and purity that can be transplanted directly into the patient’s eye, where the patient’s own RPE cells are missing or dysfunctional.
The potential benefits of replacing RPE cells include:
- RPE organization
- Drusen reduction
- Photoreceptor recovery
- Preserved or improved sight
The FDA has granted OpRegen with Orphan Drug and Fast Track Designations and, as such, is on an expedited regulatory path that includes the ability for increased interfacing with the FDA during clinical development and enhanced favorability for marketing approval.
AMD affects more than 30 million people worldwide and approximately 1.6 million people are newly diagnosed annually in the U.S.1 It is the leading cause of vision loss in people over the age of 60 in the developed world. There are two forms of AMD: “wet-AMD,” which affects only 10% of patients and “dry-AMD,” which affects 90% of patients. Currently, there are only two FDA-approved therapies for the less common wet-AMD, yet they constitute an estimated $6 billion dollar market.2
There are no FDA approved medical therapies for the 90 percent of AMD patients who suffer from the dry form. We believe one of the most promising future therapies for dry-AMD is the replacement of the layer of damaged RPE cells that support and nourish the retina.
Sources: (1) Company compilation of published information (articles, news releases, SEC filings), analyst reports; and (2) 2016 product sales summary based on publicly reported revenue figures for Lucentis and Eylea
OpRegen® is currently being tested in a Phase I/IIa clinical trial for the treatment of dry-AMD with GA. OpRegen® is a cell-based product composed of retinal pigment epithelial (RPE) cells, derived from human embryonic stem cells (hESC) and administered as a cell suspension in ophthalmic Balanced Salt Solution Plus (BSS Plus).
Phase I/IIa Clinical Trial Highlights
- OpRegen® has been well-tolerated, shows signs of structural improvement in the retina, and decreases in drusen density in some patients
- Improvements or possible restorations of the ellipsoid zone and RPE layers have persisted.
- The photoreceptor layer and ellipsoid zone assumed a more regular structural appearance in areas of the transition zone where OpRegen® was administered
- Early data from patients with earlier-stage dry-AMD is encouraging
- Structural improvement within the retina
- Evidence of the continued presence of the transplanted cells
- Some improvements in visual acuity recorded
Importantly, in this safety-focused study, no unexpected ocular adverse effects have been observed and those events expected to occur based on the procedures involved in OpRegen administration, such as vitrectomy, have been mild in severity. For more details about the Phase I/IIa study, please see data presented at the 2018 American Academy of Ophthalmology Annual Meeting.
This is a dose-escalating Phase I/IIa clinical study, designed to evaluate the safety and tolerability of OpRegen® transplantation to patients. The study includes also initial exploration of efficacy. A total of approximately 24 subjects will be enrolled, aged 50 years and older, with non-neovascular (dry) AMD, who have funduscopic findings of GA in the macula, with absence of additional concomitant ocular disorders. Subjects are divided into four cohorts, according to their best corrected visual acuity (BCVA) and administered OpRegen dose. Twelve legally blind subjects with best corrected visual acuity of 20/200 or have been enrolled in first three cohorts and twelve subjects with best corrected visual acuity of 20/64 and 20/250 will be enrolled into the fourth cohort of the study.
Primary outcome measures in the study include: (i) incidence and frequency of treatment emergent adverse events (evaluated 12 months post transplantation); and (ii) treatment emergent changes of clinical and ophthalmological parameters (evaluated 12 months post transplantation). The parameters will be measured via different modalities, such as vital signs and ocular imaging and captured as adverse events. Secondary outcome measures in the study include: (i) change in GA lesion area (evaluated 12 months post transplantation), performed based on available imaging data by a central reading center; change in visual acuity (evaluated 12 months post transplantation), measured by ETDRS chart; (iii) change in Quality of Life (evaluated 12 months post transplantation), measured from baseline.
Subretinal Delivery Partnership
In January 2019, BioTime entered into an exclusive partnership with Orbit Biomedical Ltd. to assess their approved Orbit Subretinal Delivery System, a vitrectomy-free delivery device for administration of OpRegen® within the ongoing Phase I/IIa clinical trial.
Many of the adverse effects that are observed in subretinal procedures are related to the delivery technique utilized during the surgery. The Orbit Subretinal Delivery System allows for access to the subretinal space via a suprachroidal approach without creating a hole in the retina and compromising its structural integrity. We believe that the use of this device could dramatically decrease the number of adverse effects as well as significantly improve dose control of cells in our clinical trials.
Dosing of the first patient with the Orbit Subretinal Delivery System device in the ongoing Phase I/II clinical study of OpRegen® for the treatment of dry-AMD is planned for Q2 2019.
OpRegen is comprised of specialized retina cells which were derived from a cell line that is listed on the National Institutes of Health (NIH) Registry and are eligible for use in NIH funded research.