Regenxbio Announces Additional Positive Interim Phase 1/2a Trial Update for RGX-314 for the Treatment of Wet AMD
Regenxbio announced interim data from the ongoing phase 1/2a trial of RGX-314 for the treatment of wet age-related macular degeneration (AMD). The results were presented by Jeffrey S. Heier, MD, Co-President and Director of Retina Research at Ophthalmic Consultants of Boston and primary investigator for the trial, in a podium presentation at the Retina Subspecialty Day program of the American Academy of Ophthalmology (AAO) 2019 Annual Meeting in San Francisco.
“Today’s interim update from the RGX-314 phase 1/2a dose escalation study further demonstrates the significant reduction in anti-VEGF treatment burden and encouraging improvement or maintenance of effects on vision and retinal thickness in the three higher dose cohorts,” Dr. Heier said in a company news release. “These effects are especially important as subjects in this study had been previously treated with chronic and burdensome anti-VEGF injections over several years, highlighting the severity of their disease. Today’s results further support the potential of RGX-314 gene therapy to have meaningful and durable effects in patients following a one-time intervention.”
Detailed study findings, including those presented by Dr. Heier at AAO 2019, are available under the Presentations & Publications page in the Media section of the company’s website located at www.regenxbio.com.
Study Design and Safety
In the phase 1/2a trial of RGX-314, 42 subjects with severe wet AMD requiring frequent anti-vascular endothelial growth factor (anti-VEGF) injections have been treated across five dose cohorts, with doses ranging from 3×109 GC/eye to 2.5×1011 GC/eye. Subjects were enrolled into all dose cohorts independent of their neutralizing antibody titers to AAV and did not receive prophylactic immune suppressive oral corticosteroid therapy before or after administration of RGX-314.
Subjects in the study are being assessed each month, with long-term follow-up continuing for 24 months. Assessments for the study include reduction in anti-VEGF intravitreal injections, change in vision measured by Best Corrected Visual Acuity (BCVA), change in central retinal thickness (CRT) measured by spectral domain optical coherence tomography (SD-OCT), and protein expression levels as measured from aqueous samples by electrochemiluminescence immunoassay (ECL).
As of October 9, 2019, RGX-314 continues to be well-tolerated across all cohorts, with no drug-related serious adverse events (SAEs) reported. Fifteen SAEs that were not related to RGX-314, including two ocular procedure-related SAEs, were reported in 9 subjects. There have been no reports of clinically-determined immune responses, drug-related ocular inflammation, or post-surgical inflammation beyond what is expected following routine vitrectomy.
Summary of Data for Cohorts 4 and 5
Today’s interim update includes data as of October 9, 2019 for Cohorts 4 and 5, which enrolled 12 subjects each, at doses of 1.6×1011 GC/eye and 2.5×1011 GC/eye, respectively. All 12 subjects in Cohort 4 reached 6 months of follow-up, and subjects in Cohort 5 reached 5 or 6 months of follow-up as of the data cut-off, with the exception of one subject who discontinued from the study at 4 months.1
Subjects in Cohort 5 on average had a meaningful reduction in anti-VEGF treatment burden, with 9 out of 12 (75%) subjects remaining anti-VEGF injection-free as of the data cut-off. Across the 12 subjects, there was a mean of 0.8 injections through 5 or 6 months following administration of RGX-314, a reduction of over 80% from the mean annualized injection rate during the 12 months prior to administration of RGX-314. Importantly, subjects in Cohort 5 improved visual acuity and decreased retinal thickness, with a mean BCVA change of +4 letters and a mean change in CRT of -68µm after one-time administration of RGX-314. The 9 subjects who were anti-VEGF injection-free after administration of RGX-314 showed a mean BCVA improvement of +5 letters, and a mean improvement in CRT of -80µm.
Subjects in Cohort 4 on average also had a meaningful reduction in anti-VEGF treatment burden, with 5 out of 12 (42%) subjects receiving no anti-VEGF injections in 6 months following administration of RGX-314. Across the 12 subjects in the cohort, there was a mean of 2.2 injections over 6 months following administration of RGX-314, a reduction of over 50% from the mean annualized injection rate during the 12 months prior to administration of RGX-314. Subjects in Cohort 4 maintained visual acuity and decreased retinal thickness, with a mean BCVA change of +2 letters, and a mean change in CRT of -42 µm. The 5 subjects who did not receive anti-VEGF injections after administration of RGX-314 showed a mean BCVA change of +2 letters, and a mean improvement in CRT of -61µm.
Intraocular RGX-314 protein expression levels increased in a dose-dependent manner when measured at approximately one month after administration of RGX-314; the mean protein expression level in Cohort 4 was 249.4 ng/ml, and the mean protein expression level in Cohort 5 was 376.0 ng/ml.
Summary of Long-Term Data for Cohort 3
Subjects in Cohort 3 continue to demonstrate long-term reductions in anti-VEGF treatment burden over 1.5 years. Importantly, 3 out of 6 subjects (50%) continue to remain anti-VEGF injection-free at 1.5 years. The 6 subjects across the cohort demonstrated a mean annualized rate of 2.6 anti-VEGF injections following administration of RGX-314, a reduction of over 50% from the mean annualized injection rate during the 12 months prior administration of RGX-314.
Positive long-term efficacy signals were sustained through 1.5 years in Cohort 3, including a mean BCVA improvement of +9 letters and a mean change in CRT of -40 µm. Notably, in the three patients who have remained anti-VEGF injection free at 1.5 years, the increase from baseline BCVA was +11 letters and the mean change in CRT was -21 µm.
“Frequent anti-VEGF injections have been shown to reduce the risk of blindness in subjects with wet AMD, but real-world evidence shows that people lose vision over time due to non-compliance. The notable reduction in anti-VEGF treatments seen after a single administration of the highest dose of RGX-314 in Cohort 5 is particularly encouraging, given the severity of the disease and the high treatment burden for these enrolled subjects prior to administration of RGX-314,” said Steve Pakola, M.D., Chief Medical Officer of Regenxbio. “We look forward to our anticipated start of the Phase IIb trial in subjects with wet AMD by the end of this year.”