REGENXBIO Announces Additional Positive Interim Phase I/IIa Trial Update for RGX-314 for the Treatment of Wet AMD at the American Academy of Ophthalmology 2019 Annual Meeting
"Today's interim update from the RGX-314 Phase I/IIa 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," said Dr. Heier. "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 I/IIa 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 3x109 GC/eye to 2.5x1011 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).
Summary of Data for Cohorts 4 and 5
Today's interim update includes data as of
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
RGX-314 is being developed as a potential one-time treatment for wet age-related macular degeneration (wet AMD), diabetic retinopathy (DR), and other additional chronic retinal conditions treated with anti-VEGF. RGX-314 consists of the NAV AAV8 vector encoding an antibody fragment which inhibits VEGF, modifying the pathway for formation of new leaky blood vessels which lead to retinal fluid accumulation and vision loss.
About the Phase I/IIa Clinical Trial of RGX-314
RGX‑314 is being evaluated in a Phase I/IIa, multi-center, open-label, multiple-cohort, dose‑escalation study in adult subjects with wet AMD in
About Wet AMD
Wet AMD is characterized by loss of vision due to new, leaky blood vessel formation in the retina. Wet AMD is a significant cause of vision loss in
This press release includes "forward-looking statements," within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. These statements express a belief, expectation or intention and are generally accompanied by words that convey projected future events or outcomes such as "believe," "may," "will," "estimate," "continue," "anticipate," "design," "intend," "expect," "could," "plan," "potential," "predict," "seek," "should," "would" or by variations of such words or by similar expressions. The forward-looking statements include statements relating to, among other things,
1 This subject died 4.5 months after the administration of RGX-314 as a result of the subject's underlying disease, which was assessed to be unrelated to RGX-314. At the time of the death, the subject was free of anti-VEGF injections.
Investor Relations and Corporate Communications
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