REGENXBIO Announces Additional Positive Long-term and Interim Phase I/IIa Trial Update for RGX-314 for the Treatment of Wet AMD
- RGX-314 continues to be well-tolerated at all dose levels
- Long-term, durable treatment effect demonstrated over two years in Cohort 3
- Mean improvement in vision (+14 letters) and stable retinal thickness (+2 µm)
- 50% of patients (3/6) remain anti-VEGF injection-free over two years
- 67% of patients (4/6) are anti-VEGF injection-free from nine months to two years
- Stable intraocular RGX-314 protein expression over two years
- 73% of patients (8/11) in Cohort 5 remain anti-VEGF injection-free over nine months
- Intraocular RGX-314 protein levels at six months demonstrate dose-dependent expression across cohorts
- Company on track to provide one-year data from Cohorts 4 & 5 in mid-2020 and initiate RGX-314 subretinal delivery pivotal program in 2H 2020
- Webcast conference call to be hosted
Wednesday, April 22at 8:30 a.m. ETfeaturing wet AMD Key Opinion Leaders, Allen C. Ho, M.D., Robert Avery, M.D., and Peter Campochiaro, M.D.
"I am impressed by the overall outcomes in patients after a one-time administration of RGX-314. I believe that RGX-314 is the leading gene therapy program for a major retinal disease such as wet AMD and could be an important potential one-time treatment option for AMD patients who require frequent and burdensome anti-VEGF injections. Real-world evidence demonstrates that patients lose vision over time with our current standard of care and incur significant treatment burden with frequent clinic visits and injections," said
"The clinical profile of RGX-314 appears very promising as a one-time treatment strategy for wet AMD as we continue to learn about the consistent and durable effects of our anti-VEGF gene therapy," added
Study Design and Safety
In the Phase I/IIa trial of RGX-314, 42 patients with severe wet AMD requiring frequent anti-vascular endothelial growth factor (anti-VEGF) injections were treated across five dose cohorts, with doses ranging from 3x109 GC/eye to 2.5x1011 GC/eye. Patients 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.
Patients in the study are being assessed each month for 24 months and will receive safety follow-up for five years after RGX-314 administration. Efficacy assessments for the study include reduction in anti-VEGF intravitreal injections, change in vision as measured by Best Corrected Visual Acuity (BCVA), change in central retinal thickness (CRT) as measured by spectral domain optical coherence tomography (SD-OCT), and protein expression levels as measured from aqueous samples by electrochemiluminescence immunoassay (ECL).
Across all 42 patients in the study, the most common nonserious adverse events in the study eye were generally assessed as mild (90%). These included post-operative conjunctival hemorrhage (69% of patients), post-operative inflammation (36% of patients), eye irritation (17% of patients), eye pain (17% of patients), and post-operative visual acuity reduction (17% of patients). In 67% of patients across all cohorts, and in 83% of patients in Cohorts 3-5, mild to moderate retinal pigmentary changes were observed on imaging, the majority of which were in the peripheral inferior retina. There was no evidence of clinical symptoms or changes to visual acuity related to retinal pigmentary changes. Retinal hemorrhage was observed in 17% of patients and is an anticipated event in patients with severe wet AMD.
Summary of Long-term Data for Cohort 3 Over Two Years
Positive long-term potential efficacy signals were sustained over two years in Cohort 3.The mean change in visual acuity across all six patients in Cohort 3 was markedly improved over two years, with a mean BCVA improvement of +14 letters, and the mean change in CRT was stable, with an increase of +2 µm.
Patients in Cohort 3 also demonstrated long-term reductions in anti-VEGF treatment burden over two years with a mean annualized rate of 2.8 anti-VEGF injections after administration of RGX-314, which is a reduction of over 60% from the mean annualized injection rate during the twelve months prior to administration of RGX-314. Three out of six (50%) patients received no anti-VEGF injections over two years following one-time administration of RGX-314. One patient received four anti-VEGF injections after RGX-314 administration and then did not receive anti-VEGF injections from nine months through two years.
The four patients who did not receive anti-VEGF injections after nine months demonstrated a mean BCVA improvement of +14 letters, with a range of +6 letters to +25 letters. In addition, these patients had stable retinal thickness with a mean change of +9 µm.
Additionally, long-term intraocular RGX-314 protein expression was stable in patients in Cohort 3 over two years. The mean RGX-314 protein expression level in Cohort 3 was 227.2 ng/ml at two years, compared to 217.8 ng/ml at six months. The mean RGX-314 protein expression level in the four patients who did not receive anti-VEGF injections after nine months was 291.7 ng/ml at two years, compared to 273.6 ng/ml at six months.
Summary of Data for Cohorts 4 and 5
Consistent with previous results, intraocular RGX-314 protein expression levels increased in a dose-dependent manner across cohorts when measured at six months after administration of RGX-314; the mean protein expression level in Cohort 4 and Cohort 5 was 653.6 ng/ml and 848.7 ng/ml, respectively.
Patients in Cohort 5 continued to demonstrate a meaningful reduction in anti-VEGF treatment burden over nine months following administration of RGX-314, with 8/11 (73%) patients remaining anti-VEGF injection-free, and a reduction across the cohort of over 80% from the mean annualized injection rate during the 12 months prior to RGX-314 administration.
In connection with this announcement,
To access a live or recorded webcast of the call and accompanying slides, please visit the "Investors" section of the
RGX-314 is being developed as a potential one-time treatment for wet AMD, diabetic retinopathy, and other additional chronic retinal conditions treated with anti-VEGF. RGX-314 consists of the NAV AAV8 vector encoding an antibody fragment which is designed to inhibit 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 patients 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
About REGENXBIO Inc.
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,
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