ROCKVILLE, Md., Feb. 16, 2021 /PRNewswire/ --
- RGX-314 using subretinal delivery continues to be generally
well-tolerated at all dose levels
- Positive interim update from Cohorts 4 and 5 at 1.5 years
after RGX-314 administration
-
- Durable treatment effect observed with stable visual acuity,
decreased retinal thickness, and reductions in anti-VEGF injection
burden
- Long-term, durable treatment effect over three years
demonstrated in Cohort 3
-
- Mean improvement in vision and stable retinal
thickness
- 50% of patients (3/6) remain anti-VEGF injection-free over
three years; 67% of patients (4/6) are anti-VEGF injection-free
from nine months to three years
- ATMOSPHERE™, the first of two planned pivotal trials for
RGX-314, is active and enrolling
REGENXBIO Inc. (Nasdaq: RGNX) reported at the Angiogenesis,
Exudation, and Degeneration 2021 conference additional positive
interim data from Cohorts 4 and 5 of its RGX-314 Phase I/IIa trial
for the treatment of wet age-related macular degeneration (wet
AMD), and Cohort 3 of its Long-Term Follow-Up (LTFU) study. RGX-314
is a potential best-in-class, one-time gene therapy for the
treatment of wet AMD.
"The continued durability of treatment effect up to three years
after RGX-314 administration highlights the potential of RGX-314 as
a one-time treatment option for patients with wet AMD. The results
from the Phase I/IIa trial of RGX-314 using subretinal delivery
have informed the key design elements of our pivotal program, in
which we plan to conduct two randomized, well-controlled clinical
trials, enrolling approximately 700 patients total," said
Steve Pakola, M.D., Chief Medical
Officer of REGENXBIO.
"I am excited about this data out to three years, which
demonstrates that one-time treatment with RGX-314 has the potential
to result in long-term stability to improvement of visual acuity
outcomes and retinal anatomy, while alleviating treatment burden,"
said Allen C. Ho, M.D., Director of
Retina Research at Wills Eye Hospital and Mid Atlantic Retina and
investigator surgeon in the RGX-314 clinical trials. "In our
practice, and as reported by multiple real-world studies, we see
many patients losing vision due to lack of compliance with standard
of care, which requires frequent anti-VEGF injections. I look
forward to further evaluating the effects of RGX-314 in
ATMOSPHERETM, the first pivotal trial of a gene therapy
for the treatment of wet AMD."
Study Design and Safety Update from Phase I/IIa Trial of
RGX-314 for the Treatment of Wet AMD Using Subretinal
Delivery
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.
As of January 22, 2021, RGX-314
continued to be generally well-tolerated across all cohorts, with
20 serious adverse events (SAEs) reported in 13 patients, including
one possibly drug-related SAE of significant decrease in vision in
Cohort 5. The most common nonserious adverse events in the eye were
generally assessed as mild (87%). 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 through 5, retinal pigmentary
changes were observed on imaging, the majority of which were in the
peripheral inferior retina. Retinal hemorrhage was observed in 26%
of patients and is an anticipated event in patients with severe wet
AMD. 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 update includes data from Cohorts 4 and 5 as of
January 22, 2021. Each cohort
enrolled 12 patients each at doses of 1.6x1011 GC/eye
and 2.5x1011 GC/eye, respectively.
Patients in Cohorts 4 and 5 at 1.5 years after administration of
RGX-314 demonstrated stable visual acuity with a mean Best
Corrected Visual Acuity (BCVA) change of +1 letters and -1 letters
from baseline, respectively, as well as decreased central retinal
thickness (CRT), with a mean change of -46 µm and -93 µm,
respectively.
There was a meaningful reduction in anti-VEGF treatment burden
in both Cohorts 4 and 5 compared to the mean annualized injection
rate during the 12 months prior to RGX-314 administration. Patients
in Cohort 4 received a mean of 4.4 injections over 1.5 years
following administration of RGX-314, a 58.3% reduction in anti-VEGF
treatment burden. Patients in Cohort 5 received a mean of 1.7
injections over 1.5 years following administration of RGX-314, a
reduction in anti-VEGF treatment burden of 81.2%.
In Cohort 4, four out of 12 (33%) patients have received no
anti-VEGF injections after six months following RGX-314
administration and demonstrated a mean BCVA change from baseline of
+2 letters at 1.5 years. Eight out of 11 (73%) patients have
received no anti-VEGF injections after six months following RGX-314
administration and demonstrated a mean BCVA change from baseline of
-2 letters at 1.5 years.
Summary of Long-Term Follow-Up (LTFU) Study Data
Following the Phase I/IIa trial, patients are encouraged to
enroll in a LTFU study to assess safety and efficacy up to five
years after RGX-314 administration. Patients in the LTFU study have
scheduled visits every six months for the first year and then
annual visits until the end of the study. Patient management is per
physician discretion. Data collected during the scheduled study
visits include safety, BCVA, and CRT. In addition, chart reviews
are conducted at each scheduled study visit to collect the number
of retina specialist visits and anti-VEGF injections each patient
has received since the prior scheduled study visit.
As of January 22, 2021, RGX-314
continued to be generally well-tolerated in patients enrolled in
the LTFU study, with no new drug-related ocular adverse events
reported.
All six patients from Cohort 3 of the Phase I/IIa trial enrolled
in the LTFU study, and long-term treatment effect was demonstrated
over three years. These patients demonstrated a mean BCVA
improvement of +12 letters from baseline at three years. Retinal
anatomy as measured by machine-read CRT remained stable at three
years compared to the two-year timepoint.
Patients also demonstrated long-term reductions in anti-VEGF
treatment burden over three years with a mean annualized rate of
2.4 anti-VEGF injections after administration of RGX-314, which is
a reduction of 66.7% from the mean annualized injection rate during
the 12 months prior to administration of RGX-314. Three out of six
(50%) patients received no anti-VEGF injections over three years
following one-time administration of RGX-314. Four out of six (67%)
patients have received no anti-VEGF injections from nine months to
three years after RGX-314 administration. The four patients who did
not receive anti-VEGF injections after nine months demonstrated a
mean BCVA improvement from baseline of +11 letters at three
years.
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 the United
States, Europe and
Japan, with up to 2 million people
living with wet AMD in these geographies alone. Current anti-VEGF
therapies have significantly changed the landscape for treatment of
wet AMD, becoming the standard of care due to their ability to
prevent progression of vision loss in the majority of patients.
These therapies, however, require life-long intraocular injections,
typically repeated every four to 12 weeks in frequency, to maintain
efficacy. Due to the burden of treatment, patients often experience
a decline in vision with reduced frequency of treatment over
time.
About RGX-314
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.
REGENXBIO is advancing two separate routes of administration of
RGX-314 to the eye, through a standardized subretinal delivery
procedure as well as delivery to the suprachoroidal space.
REGENXBIO has licensed certain exclusive rights to the SCS
Microinjector® from Clearside Biomedical, Inc. to
deliver gene therapy treatments to the suprachoroidal space of the
eye.
About the Phase I/IIa Clinical Trial of RGX-314 and Long-Term
Follow-Up Study
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 the United
States. The study includes patients previously treated for
wet AMD who are responsive to anti-VEGF therapy. The study is
designed to evaluate five escalating doses of RGX-314, with six
patients in the first three dose cohorts and 12 patients in the
fourth and fifth dose cohorts. 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.
The primary endpoint of the study is safety at 6 months following
administration of RGX-314. Secondary endpoints include visual
acuity, retinal thickness on SD–OCT, ocular RGX-314 protein
expression, and the need for additional anti-VEGF therapy.
Following completion of the primary study period, patients enter a
follow-up period and will continue to be assessed until week 106
for long-term safety and durability of effect. After completion of
the Phase I/IIa clinical trial, patients are encouraged to enter a
Long-Term Follow-Up study to continue to follow safety and efficacy
for a total of 5 years following administration of RGX-314.
About ATMOSPHERE™
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 the United States, with
over 100 retinal surgeons.
About REGENXBIO Inc.
REGENXBIO is a leading clinical-stage biotechnology company
seeking to improve lives through the curative potential of gene
therapy. REGENXBIO's NAV® Technology Platform, a
proprietary adeno-associated virus (AAV) gene delivery platform,
consists of exclusive rights to more than 100 novel AAV vectors,
including AAV7, AAV8, AAV9 and AAVrh10. REGENXBIO and its
third-party NAV Technology Platform Licensees are applying the NAV
Technology Platform in the development of a broad pipeline of
candidates in multiple therapeutic areas.
Forward-Looking Statements
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, REGENXBIO's future operations and
clinical trials. REGENXBIO has based these forward-looking
statements on its current expectations and assumptions and analyses
made by REGENXBIO in light of its experience and its perception of
historical trends, current conditions and expected future
developments, as well as other factors REGENXBIO believes are
appropriate under the circumstances. However, whether actual
results and developments will conform with REGENXBIO's expectations
and predictions is subject to a number of risks and uncertainties,
including the timing of enrollment, commencement and completion and
the success of clinical trials conducted by REGENXBIO, its
licensees and its partners, the timing of commencement and
completion and the success of preclinical studies conducted by
REGENXBIO and its development partners, the timely development and
launch of new products, the ability to obtain and maintain
regulatory approval of product candidates, the ability to
accurately predict how long REGENXBIO's existing cash resources
will be sufficient to fund its anticipated operating expenses, the
ability to obtain and maintain intellectual property protection for
product candidates and technology, trends and challenges in the
business and markets in which REGENXBIO operates, the size and
growth of potential markets for product candidates and the ability
to serve those markets, the rate and degree of acceptance of
product candidates, the impact of the COVID-19 pandemic or similar
public health crises on REGENXBIO's business, and other factors,
many of which are beyond the control of REGENXBIO. Refer to the
"Risk Factors" and "Management's Discussion and Analysis of
Financial Condition and Results of Operations" sections of
REGENXBIO's Annual Report on Form 10-K for the year ended
December 31, 2019, and comparable
"risk factors" sections of REGENXBIO's Quarterly Reports on Form
10-Q and other filings, which have been filed with the U.S.
Securities and Exchange Commission (SEC) and are available on the
SEC's website at www.sec.gov. All of the forward-looking statements
made in this press release are expressly qualified by the
cautionary statements contained or referred to herein. The actual
results or developments anticipated may not be realized or, even if
substantially realized, they may not have the expected consequences
to or effects on REGENXBIO or its businesses or operations. Such
statements are not guarantees of future performance and actual
results or developments may differ materially from those projected
in the forward-looking statements. Readers are cautioned not to
rely too heavily on the forward-looking statements contained in
this press release. These forward-looking statements speak only as
of the date of this press release. REGENXBIO does not undertake any
obligation, and specifically declines any obligation, to update or
revise any forward-looking statements, whether as a result of new
information, future events or otherwise.
SCS Microinjector® is a trademark of Clearside
Biomedical, Inc. All other trademarks referenced herein are
registered trademarks of REGENXBIO.
Contacts:
Tricia Truehart
Investor Relations and Corporate Communications
347-926-7709
ttruehart@regenxbio.com
Investors:
Brendan Burns,
212-600-1902
brendan@argotpartners.com
Media:
David Rosen, 212-600-1902
david.rosen@argotpartners.com
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