REGENXBIO Announces Update on RGX-314 and Pivotal Program for the Treatment of Wet AMD and New Gene Therapy Program for the Treatment of Duchenne Muscular Dystrophy
- Pivotal program for RGX-314, potential best-in-class, one-time gene therapy for the treatment of wet AMD, is active and expected to support BLA filing in 2024
- Recently completed an End of Phase 2 meeting with FDA
- First of two planned pivotal trials is active
- Pivotal program expected to enroll a total of approximately 700 patients
- Clear path for cGMP manufacturing process to support BLA
- Phase II trials for RGX-314 utilizing in-office, suprachoroidal delivery on-going; enrollment complete in first cohort of AAVIATE trial
- IND filing expected in mid-2021 for a novel, advanced microdystrophin gene therapy for the treatment of Duchenne Muscular Dystrophy
- Expects to end 2020 with between $515 million and $530 million in cash, cash equivalents and marketable securities
"2020 was a very productive year at
"We are pleased to have reached alignment with the FDA on key elements of our pivotal program for the treatment of wet AMD. Our plan allows us to further accelerate the clinical development of RGX-314 towards the goal of a BLA filing in 2024 and we have already begun site activation and patient screening for our first planned pivotal trial," said
- ATMOSPHERE will evaluate the efficacy and safety of RGX-314 in patients with wet AMD.
- The trial will enroll approximately 300 patients across two RGX-314 dose arms versus ranibizumab. The primary endpoint of the trial is non-inferiority to ranibizumab based on change from baseline in Best Corrected Visual Acuity (BCVA) at one year.
- Site activation is ongoing and
REGENXBIOexpects to begin dosing patients in this trial in the first quarter of 2021.
- The second pivotal trial is expected to be similar in design to ATMOSPHERE and
REGENXBIOplans to initiate the trial in the second half of 2021.
- The trial is expected to have two RGX-314 dose arms versus aflibercept, and the planned primary endpoint is non-inferiority to aflibercept based on the change from baseline in BCVA at one year.
- In addition, based on discussions with FDA,
REGENXBIObelieves it has a clear path to support cGMP commercial-ready manufacturing plans in the pivotal program. REGENXBIOhas initiated its pivotal program using cGMP material produced from its existing manufacturing process and has agreement with the FDA to incorporate its scalable suspension cell culture manufacturing process to support future commercialization, upon completion of a bridging study and the pivotal trials. The bridging study is expected to initiate in the first half of 2021.
Suprachoroidal Delivery of RGX-314 for the Treatment of Wet AMD and Diabetic Retinopathy (DR)
REGENXBIOhas completed enrollment of patients in Cohort 1 of AAVIATE™, a Phase II trial for the treatment of wet AMD. REGENXBIOplans to report interim data from Cohort 1 in the third quarter of 2021.
- Enrollment of patients in Cohort 2 is expected to begin in the first quarter of 2021.
- Enrollment of patients continues in Cohort 1 for ALTITUDE™, a Phase II trial for the treatment of DR.
REGENXBIOexpects to report initial data from this trial in 2021.
- As of
December 31, 2020, suprachoroidal delivery of RGX-314 in AAVIATE and ALTITUDE is reported to be generally well-tolerated, with no evidence of inflammation.
New Program for the Treatment of Duchenne Muscular Dystrophy
"DMD is a severe, degenerative disease affecting thousands of children worldwide. It is caused by mutations of the gene which encodes dystrophin, a protein necessary for muscle cell strength and function, and innovation and development of potential new treatment options for patients with DMD has been a goal for the gene therapy field for many years," said
- RGX-202 is designed to deliver a novel microdystrophin transgene which includes an extended coding region of the C-Terminal (CT) domain found in naturally occurring dystrophin, as well as other fundamental improvements.
- Presence of the CT domain has been shown to recruit several key proteins to the muscle cell membrane, leading to improved muscle resistance to contraction-induced muscle damage in dystrophic mice.1
- Additional design features, including codon optimization and reduction of CpG content, may potentially improve gene expression, increase translational efficiency and reduce immunogenicity.
- RGX-202 is designed to use the NAV AAV8 vector, a vector used in numerous clinical trials, and a well-characterized muscle specific promoter (Spc5-12) to support the delivery and targeted expression of genes throughout skeletal and heart muscle.
- Proof of concept data from preclinical studies of RGX-202 in the mdx mouse model of DMD demonstrates broad and robust expression of microdystrophin in muscle, recruitment of key proteins to the muscle cells, improvements in muscle histology, as well as meaningful increases in muscle strength and function.
- Commercial-scale cGMP material has already been produced at 1000L capacity using
REGENXBIO'ssuspension cell culture manufacturing process and will be used in the clinical development of RGX-202.
- Investigational New Drug (IND) application enabling studies are being completed and
REGENXBIOexpects to submit an IND to the FDA in mid-2021.
The design of the new RGX-202 microdystrophin transgene is based on innovative vector engineering by
"The data from dystrophic laboratory trials suggest that a gene therapy delivering a microdystrophin gene incorporating an extended coding region from the C-Terminal Domain such as RGX-202 may provide substantial added muscle function for patients with DMD. A blend of the innovative science applied to microdystrophin gene design, and an AAV vector that is well-established, makes this new approach very promising," said Professor
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
RGX-314 is being developed as a potential one-time treatment for wet AMD, diabetic retinopathy, and other chronic retinal conditions. RGX-314 consists of the NAV AAV8 vector, which encodes an antibody fragment designed to inhibit vascular endothelial growth factor (VEGF). RGX-314 is believed to inhibit the VEGF pathway by which new, leaky blood vessels grow and contribute to the accumulation of fluid in the retina.
ATMOSPHERE is a multi-center, randomized, active-controlled trial to evaluate the efficacy and safety of a single-administration of RGX-314 versus standard of care in patients with wet AMD. The trial is designed to enroll 300 patients at a 1:1:1 ratio across two RGX-314 dose arms (6.4x1010 genome copies (GC)/eye and 1.3x1011 GC/eye delivered subretinally) and an active control arm of monthly intravitreal injections of ranibizumab (0.5 mg/eye). The primary endpoint of the trial is non-inferiority to ranibizumab based on change from baseline in Best Corrected Visual Acuity (BCVA) at 54 weeks. Secondary endpoints of the trial include safety and tolerability, change in central retinal thickness (CRT) and need for supplemental anti-VEGF injections. Patient selection criteria will include patients with wet AMD who are responsive to anti-VEGF treatment and will be independent of preexisting neutralizing antibody status. Patients will not receive prophylactic immune suppressive corticosteroid therapy before or after administration of RGX-314. The trial will be conducted at approximately 60 clinical sites based in
AAVIATE is a multi-center, open-label, randomized, active-controlled, dose-escalation trial that will evaluate the efficacy, safety and tolerability of suprachoroidal delivery of RGX-314 using the SCS Microinjector, a targeted, in-office route of administration. The trial is expected to enroll approximately 40 patients with severe wet AMD across two cohorts. Patients in each cohort will be randomized to receive RGX-314 versus monthly 0.5 mg ranibizumab intravitreal injection at a 3:1 ratio, and two dose levels of RGX-314 will be evaluated: 2.5x1011 GC/eye and 5x1011 GC/eye. Patients will not receive prophylactic immune suppressive corticosteroid therapy before or after administration of RGX-314. The primary endpoint of the trial is mean change in vision in patients dosed with RGX-314, as measured by best corrected visual acuity (BCVA), at Week 40 from baseline, compared to patients receiving monthly injections of ranibizumab. Other endpoints include mean change in central retinal thickness (CRT) and number of anti-VEGF intravitreal injections received following administration of RGX-314.
ALTITUDE is a multi-center, open label, randomized, controlled dose-escalation trial that will evaluate the efficacy, safety and tolerability of suprachoroidal delivery of RGX-314. The trial is expected to enroll approximately 40 patients with DR across two cohorts. Patients will be randomized to receive RGX-314 versus observational control at a 3:1 ratio, and two dose levels of RGX-314 will be evaluated: 2.5x1011 GC/eye and 5.0x1011 GC/eye. Patients will not receive prophylactic immune suppressive corticosteroid therapy before or after administration of RGX-314. The primary endpoint of the trial is the proportion of patients that improve in DR severity based on the Early Treatment Diabetic Retinopathy Study-Diabetic Retinopathy Severity Scale (ETDRS-DRSS) at 48 weeks. Other endpoints include safety and development of DR-related ocular complications.
About Duchenne Muscular Dystrophy
DMD is a severe, progressive, degenerative muscle disease, affecting 1 in 3,500 to 5,000 boys born each year worldwide. DMD is caused by mutations in the DMD gene which encodes for dystrophin, a protein involved in muscle cell structure and signaling pathways. Without dystrophin, muscles throughout the body degenerate and become weak, eventually leading to loss of movement and independence, required support for breathing, cardiomyopathy and premature death.
RGX-202 is designed to deliver a novel microdystrophin transgene which retains key elements of the dystrophin protein, including an extended coding region of the C-Terminal (CT) domain found in naturally-occurring dystrophin, as well as other fundamental improvements to the transgene. Presence of the CT domain has been shown to recruit several key proteins to the muscle cell membrane, leading to improved muscle resistance to contraction-induced muscle damage in dystrophic mice. Additional design features, including codon optimization and reduction of CpG content, may potentially improve gene expression, increase translational efficiency and reduce immunogenicity. RGX-202 is designed to use the NAV AAV8 vector, a vector used in numerous clinical trials, and a well-characterized muscle specific promoter (Spc5-12) to support the delivery and targeted expression of genes throughout skeletal and heart muscle.
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,
SCS Microinjector® is a trademark of Clearside Biomedical, Inc. All other trademarks referenced herein are registered trademarks of
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1 Koo, Taeyoung et al. "Delivery of AAV2/9-microdystrophin genes incorporating helix 1 of the coiled-coil motif in the C-terminal domain of dystrophin improves muscle pathology and restores the level of α1-syntrophin and α-dystrobrevin in skeletal muscles of mdx mice." Human gene therapy vol. 22,11 (2011): 1379-88. doi:10.1089/hum.2011.020
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