OpRegen®
for Dry AMD
On December 20, 2021, Lineage entered into an exclusive worldwide collaboration and license agreement with Roche and Genentech, a member of the Roche Group, for the development and commercialization of OpRegen for the treatment of ocular disorders, including advanced dry age-related macular degeneration (dry AMD) with geographic atrophy (GA) in a transaction worth up to $670 million in addition to double digit royalties. In January 2022, Lineage received a $50 million upfront payment from Genentech.
In November 2022, Genentech launched a Phase 2a, multicenter, open-label, single arm clinical study of RG6501 (OpRegen) in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD).
Image adapted from scienceofamd.org
OpRegen is currently being evaluated in a Phase 2a study intended to optimize subretinal surgical delivery and evaluate safety and activity in up to 60 patients. The primary objectives of the study are to evaluate (i) the proportion of patients with subretinal surgical delivery of OpRegen to target regions under the retina, and (ii) to evaluate the safety of subretinal surgical delivery of OpRegen as measured by the incidence and severity of procedure-related adverse events at 3 months following surgery. A key secondary objective is to evaluate the proportion of patients with qualitative improvement in retinal structure, as determined by Optical Coherence Tomography (SD-OCT) imaging, within 3 months following surgery.
The FDA has granted OpRegen with 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.
Clinical Data
In October 2023, data was presented at the 23rd EURETINA Congress. OpRegen Phase 1/2a clinical results show evidence of rapid improvement in outer retinal structure in patients with geographic atrophy secondary to age-related macular degeneration.
23rd EURETINA Congress Highlights:
- All 5 patients enrolled in cohort 4 who had extensive coverage of the GA lesion with the surgical bleb containing OpRegen in suspension, demonstrated evidence of improvement in outer retinal structure as assessed by optical coherence tomography (OCT) within the first 3 months after treatment.
- Retinal structural improvement in the patients described above were initially observed on day 1 (n=1), day 14 (n=1), month 1 (n=2), and month 3 (n=1).
- Maintenance and/or greater improvements in retinal structure were observed over time.
- Structural improvement (as defined below) was only observed within GA lesions with extensive coverage with the surgical bleb suggesting that OpRegen RPE cells provide support to the remaining retinal cells within atrophic areas.
- These 5 patients had an average of 4.4 letter BCVA gain by 3 months and 12.8 letter BCVA gain by 1 year compared to baseline.
- OCT images were reviewed by three independent graders from the day after surgery to the start of structural improvement and subsequent follow-up visits.
- Structural improvement on OCT was qualitatively defined as meeting all pre-specified criteria including: 1) reduction in outer plexiform layer (OPL) and/or inner nuclear layer (INL) subsidence; 2) reappearance of external limiting membrane (ELM); and 3) increased hyperreflectivity and/or thickness of RPE and/or Bruch’s membrane or reduction of hypertransmission on at least two non-adjacent B scans.
- The patient who demonstrated retinal structure improvement as early as day 1 following OpRegen subretinal delivery exhibited persistence of structural improvement as measured by OCT, with resolution of areas of complete RPE and outer retinal atrophy (cRORA) features at 24 months following treatment. Durability of retinal structure improvements beyond the 12-month primary endpoint is still being evaluated in other patients.
Exploratory Objective: Onset of Structural Improvement
In Study Eyes with Extensive OpRegen Bleb Coverage (n=5)
On at least two non-adjacent B scans; the onset of improvement may be confounded by surgical bleb resolution. Follow-up mode was turned on during acquisition of these OCT scans to enforce longitudinal registration. Registration was verified manually by comparing choroidal patterns. There may be slight offset of inner retina blood vessels due to eye orientation difference during acquisition. Image courtesy of Adiel Barak, MD
Onset of Structural Improvement Within 3 Months
in All 5 Patients with Extensive Bleb Coverage
Image courtesy of Adiel Barak, MD
Preliminary Evidence of Maintenance of Structural Improvement
24 Months Post-Treatment
Case 14; CFP, color fundus photography; cRORA, complete RPE and outer retinal atrophy; RPEDC, retinal pigment epithelium drusen complex.
aELM map, binary external limiting membrane presence/absence map, green when ELM is present, dark blue when ELM is absent.
RPEDC and ELM maps are generated by Genentech EyeNotate OCT segmentation algorithm; the segmentation results are reviewed and corrected by a single masked expert grader. Image courtesy of Adiel Barak, MD
Market Opportunity
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 a 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 10-15% of patients and “dry AMD,” which affects 85-90% of patients.2
Sources: (1) Pennington and DeAngelis, Eye and Vision, 2016 3:34; (2) JM Seddon, Epidemiology of age-related macular degeneration. (AP Schachat, S Ryan eds.) Retina, 3rd ed. St. Louis, MO: Mosby; 2001;1039-50
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