After a single dose of RGX gene therapy, the mean change in BCVA was +8 letters in cohort 3 and the average number of injections over the course of 6 months was 1.3 in a phase 1 cohort study.
Many patients who have been diagnosed with wet age-related macular degeneration (wet AMD) require anti-VEGF injections to prevent blindness, but such injections have a considerable burden on these patients and their caregivers.
RGX-314 is a gene therapy being developed as an alternative one-time subretinal treatment for wet AMD by REGENXBIO. The treatment includes a NAV AAV8 vector encoding antibody fragment which is able to inhibit VEGF and delay the formation of new leaky blood vessels which lead can lead to vision loss.
The interim phase 1 data for RGX-314 was presented in a late-breaker presentation at the retina subspecialty day at the American Academy of Ophthalmology Annual Meeting 2018 in Chicago, Illinois.
The phase I study is an open-label, multiple-cohort, dose‑escalation study in adult participants with wet AMD across 7 study sites in the United States. The study has enrolled 24 participants aged 50 or older who have previously been treated for wet AMD and are responsive to anti-VEGF therapy into 1 of 4 cohorts.
The study is evaluating four different doses of RGX-314: 3 x 10^9 GC/eye (cohort 1), 1 x 10^10 GC/eye (cohort 2), 6 x 10^10 GC/eye (cohort 3), and 1.6 x 10^11 GC/eye (cohort 4).
The data presented this weekend at AAO, focused on the results of the cohort 3 data. MD Magazine® sat down with Peter Campochiaro, MD, professor of ophthalmology, director of the retinal cell and molecular laboratory at Johns Hopkins Medicine, and an investigator on the study to learn more about the gene therapy and the study.
Cohort 3 evaluated 6 patients with a median age of 80 years, 71.6 months since first anti-VEGF infection and a mean of 34.2 injections since diagnosis.
Previously presented data in August of 2018 indicated that RGX-314 was well tolerated in cohorts 1 and 2 and showed dose-dependent protein expression levels and dose-dependent reductions in anti-vascular endothelial growth factor injections along with maintenance of central retinal thickness and vision.
In this patient population of cohort 3, the investigators found that after 1 month, there was a mean protein level of 160.2 ng/ml and a median protein level of 93.1 ng/ml. After 6 months, the mean protein level was 217.8 ng/ml and the median protein level was 181.6 ng.ml, as measured from aqueous samples by electrochemiluminescence-based assay.
Data also indicate that the mean change in best corrected visual acuity (BCVA) was +8 letters in cohort 3 and the average number of injections over the course of 6 months was 1.3.
Additionally, 50% of the patients were free of anti-VEGF injections at the 6-month mark.
The primary purpose of the cohort study is to evaluate the safety and tolerability of RGX-314 at 24 weeks after a gene therapy treatment. The primary endpoints include safety and tolerability and secondary endpoints include ocular examinations, visual acuity, and the need for additional anti-VEGF therapy.
Following the third cohort, a new fourth cohort was initiated at a higher dose of 1.6 x 10^11 GC/eye, for which data has not yet been released. According to a company statement, there will be a follow-up period during which participants from all cohorts will be monitored until week 106 to assess long-term safety and durability.
The next step for RGX-314 is a phase 2 clinical trial which is expected to be designed in early 2019.
Editors note: Updated 10/28/2018 at 9:04 AM EST