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 April 2023, data was presented at the 2023 Association for Research in Vision and Ophthalmology Annual Meeting. OpRegen Phase 1/2a clinical results support the potential for OpRegen to slow, stop or reverse disease progression in geographic atrophy secondary to age-related macular degeneration.
- Preliminary evidence of outer retinal structure and visual function improvements with OpRegen was observed in patients with GA and impaired vision (Cohort 4 [n=12]):
- Patients in Cohort 4 had an average 7.6 letter gain in visual acuity at 12 months in the study eye;
- Three patients in Cohort 4 (25%) had a 15 letter or greater gain in visual acuity at 12 months in the study eye.
- Long term vision preservation with outer retinal structure improvement observed in the OpRegen treated eye persisted for up to 4 years of follow-up.
- The extent of OpRegen bleb coverage over the area of atrophy may be important to optimize patient outcomes:
- In patients with extensive OpRegen bleb coverage, maintenance or improvement of outer retina structure was observed in treated eyes compared to worsening in fellow eyes:
- Five patients in Cohort 4 who had a surgically delivered bleb containing OpRegen that extensively covered their atrophic areas and the foveal center, experienced an average 12.8 letter gain in their study eye.
- Improvement in outer retinal layers also correlated with the extent of OpRegen bleb coverage:
- Slower rates of RPE and external limiting membrane (ELM) loss were observed in OpRegen treated eyes compared to fellow untreated eyes;
- Patients with extensive OpRegen bleb coverage of the atrophic area had maintenance or improvement of RPE and ELM layers compared to patients with limited OpRegen bleb coverage.
- Resolution of complete RPE and outer retinal atrophy (cRORA) near borders of baseline GA were observed in cases with extensive coverage:
- Signs of improvement in areas of cRORA included: greater hyperreflectivity at the level of RPE/ Bruch’s membrane (BM); less choroidal hypertransmission; reduction of retinal subsidence, and greater continuity of outer retinal layers.
- OCT imaging with segmentation analysis may be advantageous in assessment of retinal integrity following OpRegen treatment:
- OCT enables quantitation of changes in RPE and outer retinal structure (such as ELM loss) not possible with FAF imaging following OpRegen subretinal delivery.
- In patients with extensive OpRegen bleb coverage, maintenance or improvement of outer retina structure was observed in treated eyes compared to worsening in fellow eyes:
Smaller Area of Atrophy (GA) Following Single Dose
Image courtesy of Miao Zhang
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