We completed an End of Phase 2 meeting with the U.S. Food and Drug
Administration, or FDA, to discuss the details of a pivotal program
to support a Biologics License Application, or BLA, for
RGX-314. Based on
discussions with the FDA, we plan to conduct two randomized,
well-controlled clinical trials to evaluate the efficacy and safety
of RGX-314 in patients with
wet AMD, and expect to enroll approximately 700 patients total. In
addition, based on our discussions with the FDA, we believe we have
a clear path to support current Good Manufacturing Practice, or
cGMP, commercial-ready manufacturing plans in the pivotal program.
We expect to submit a BLA based on these trials in 2024.
ATMOSPHERETM,
the first planned pivotal trial, 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 and patient screening
are ongoing and we expect to begin dosing patients in this trial in
the first quarter of 2021.
The second planned pivotal trial is expected to be similar in
design to ATMOSPHERE, and we plan 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.
We have completed enrollment of patients in Cohort 1 of
AAVIATETM, a
Phase II trial to evaluate the suprachoroidal delivery of
RGX-314 using the SCS
Microinjector for the treatment of wet AMD. We expect to report
interim data from Cohort 1 of this trial in the third quarter of
2021, and enrollment of patients in Cohort 2 is expected to begin
in the first quarter of 2021.
Enrollment of patients continues in Cohort 1 for
ALTITUDETM, a
Phase II trial to evaluate the suprachoroidal delivery of
RGX-314 using the SCS
Microinjector for the treatment of DR. We expect to report initial
data from this trial in 2021.
As of December 31, 2020, suprachoroidal delivery of
RGX-314 in AAVIATE and
ALTITUDE has been reported to be generally well-tolerated, with no
evidence of ocular inflammation.
RGX-202
We are developing RGX-202
for the treatment of Duchenne muscular dystrophy, or DMD, a severe,
progressive, degenerative muscle disease. 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 includes an
extended coding region of the C-Terminal, or 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. 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.