ROCKVILLE, Md., Aug. 4, 2020 /PRNewswire/ --
- Company on track to initiate RGX-314 subretinal delivery
pivotal program by the end of 2020
- RGX-314 was generally well-tolerated in 42 patients at all
dose levels in Phase I/IIa trial
- Positive interim update from Cohorts 4 and 5 at one year
informs pivotal program
-
- Durable treatment effect observed with stable to improved
visual acuity and retinal thickness
- Demonstrated meaningful reductions in anti-VEGF treatment
burden over one year
-
- 61% and 85% reduction of anti-VEGF injections in Cohorts 4
and 5, respectively
- 73% of patients (8/11) in Cohort 5 remain anti-VEGF
injection-free
- Intraocular RGX-314 protein expression levels are
dose-dependent at one year
- Phase II trial for RGX-314 for the treatment of wet AMD
using suprachoroidal delivery (AAVIATE) is active
-
- Enrollment expected to begin in Q3 2020; interim data update
from first cohort expected by end of 2020
- Company to host conference call and webcast on Tuesday, August 4 at 8:30a.m. ET, featuring wet AMD Key Opinion
Leaders, Robert Avery, M.D.,
Dante Pieramici, M.D., and
Peter Kaiser, M.D.
REGENXBIO Inc. (Nasdaq: RGNX), a leading clinical-stage
biotechnology company seeking to improve lives through the curative
potential of gene therapy based on its proprietary
NAV® Technology Platform, today reported positive
one year data from patients in Cohorts 4 and 5 of the Phase I/IIa
trial of RGX-314 for the treatment of wet age-related macular
degeneration (wet AMD). The Company plans to initiate a pivotal
program for subretinal delivery of RGX-314 in patients with wet AMD
by the end of 2020. In addition, REGENXBIO today announced that a
Phase II trial of RGX-314 for the treatment of wet AMD delivered to
the suprachoroidal space (AAVIATE) is active and expected to enroll
patients in the third quarter of 2020.
"Today's results provide further evidence of the clinical
profile of RGX-314 as a promising one-time gene therapy treatment
paradigm for patients with wet AMD," said Steve Pakola, M.D., Chief Medical Officer of
REGENXBIO. "The data demonstrated stable to improved visual acuity
and retinal thickness, as well as a meaningful reduction in
anti-VEGF injection burden, in these higher dose levels at one
year. Results from the Phase I/IIa trial will inform the design of
the pivotal program of RGX-314 in patients with wet AMD, which we
look forward to initiating by the end of this year."
Dr. Pakola continued: "I am also pleased to announce that our
AAVIATE trial, a Phase II trial of RGX-314 for the treatment of wet
AMD utilizing the SCS Microinjector, is active and we expect to
dose the first patient this quarter. The targeted, in-office
suprachoroidal delivery approach may provide additional options for
patients in all settings of patient care. We anticipate providing
an interim data update from the first cohort in late 2020."
"Based on the overall results to date from the Phase I/IIa
trial, I believe that RGX-314 has the potential to profoundly
impact all aspects of clinical management for patients with wet
AMD," said Robert Avery, M.D.,
Founder of California Retina Consultants and Research Foundation
and investigator surgeon in the Phase I/IIa RGX-314 trial. "Wet AMD
affects a large number of adults, and often results in loss of
vision over time due to non-compliance with the current standard of
care of frequent anti-VEGF injections. I am encouraged that RGX-314
has the potential to become a one-time gene therapy treatment
option for a broad range of patients."
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
long-standing 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 or supplemental immune
suppressive corticosteroid therapy for RGX-314.
Patients in the study are being assessed each month for two
years and will receive safety follow-up for five years after
RGX-314 administration. Efficacy assessments for the study include
number of 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 RGX-314 protein expression
levels as measured from aqueous samples by electrochemiluminescence
immunoassay (ECL).
As of July 13, 2020, RGX-314 was
generally well-tolerated across all cohorts. Eighteen serious
adverse events (SAEs) were reported in 11 patients, including 17
that were not related to RGX-314. One possibly drug-related SAE of
significant decrease in vision was reported in Cohort 5 at Month 11
in a patient who had retinal pigmentary changes that involved the
macula. The most common nonserious adverse events in the eye were
generally assessed as mild (77%). 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 24%
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 from Cohorts 4 and 5 of Phase I/IIa Trial of
RGX-314 for the Treatment of Wet AMD using Subretinal
Delivery
Today's update includes data from Cohorts 4 and 5 as of
July 13, 2020. Each cohort enrolled
12 patients each at doses of 1.6x1011 GC/eye and
2.5x1011 GC/eye, respectively.
Patients in Cohort 4 and Cohort 5 at one year after
administration of RGX-314 demonstrated stable visual acuity with a
mean BCVA change of +4 letters and -2 letters from baseline,
respectively, as well as decreased retinal thickness, with a mean
change in CRT of -61 µm and -79 µm, respectively.
There was a clinically significant and meaningful reduction in
anti-VEGF treatment burden in both Cohorts 4 and 5 compared to the
12 months prior to RGX-314 administration. Patients in Cohort 4
received a mean of 4.1 injections over one year following
administration of RGX-314, a 61% reduction in treatment burden.
Patients in Cohort 5 received a mean of 1.4 injections over one
year following administration of RGX-314, a reduction in treatment
burden of 85%.
In Cohort 4, three out of twelve (25%) patients received no
anti-VEGF injections over one year, and these patients demonstrated
a mean BCVA improvement of +6 letters and a mean reduction in CRT
of -62 µm at one year. In Cohort 5, eight out of the eleven (73%)
patients observed through one year have received no anti-VEGF
injections after administration of RGX-314 and these patients
demonstrated a stable mean BCVA change of 0 letters and a mean
reduction in CRT of -95 µm at one year.
Consistent with previous results, intraocular RGX-314 protein
expression levels were observed in a dose-dependent manner across
each cohort at one year after administration of RGX-314. The mean
protein expression levels in Cohort 4 and Cohort 5 were 420.9 ng/ml
and 457.5 ng/ml, respectively.
Study Design for Phase II Trial for RGX-314 for Treatment of
Wet AMD using Suprachoroidal Delivery (AAVIATE)
REGENXBIO also announced that a Phase II trial, AAVIATE, to
evaluate the suprachoroidal delivery of RGX-314 in patients with
wet AMD, will begin dosing patients in the third quarter of 2020.
AAVIATE is a multi-center, open-label, randomized,
active-controlled, dose-escalation study 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.
AAVIATE will enroll 40 patients with severe wet AMD who are
responsive to anti-VEGF treatment. Patients will be randomized to
one-time RGX-314 SCS delivery versus monthly 0.5 mg ranibizumab
intraocular 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 study is mean change in vision, as
measured by BCVA, at 40 weeks from baseline compared to monthly
ranibizumab. Other endpoints include mean change in CRT and number
of anti-VEGF intravitreal injections.
The Company expects to report interim data from the first cohort
of this trial by the end of 2020.
Conference Call
In connection with this announcement, REGENXBIO will host a
webcast and conference call with accompanying slides today at
8:30 a.m. ET. This event will feature
Robert Avery, M.D., Founder of
California Retina Consultants and Research Foundation, Dante Pieramici, M.D., Director, California
Retina Research Foundation and Partner, California Retina
Consultants, and Peter Kaiser, M.D.,
Chaney Family Endowed Chair in Ophthalmology Research and Professor
of Ophthalmology, Cleveland Clinic Lerner College of Medicine and
Cole Eye Institute.
To access a live or recorded webcast of the call and
accompanying slides, please visit the "Investors" section of the
REGENXBIO website at www.regenxbio.com. To access the live call by
phone, dial (888) 317-6003 (domestic) or (412) 317-6061
(international) and enter the passcode 6960652. The recorded
webcast will be available for approximately 30 days following the
call.
About RGX-314
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 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.
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 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 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.
Contacts:
Tricia Truehart
Investor Relations and Corporate Communications
347-926-7709
Investors:
Eleanor Barisser, 212-600-1902
eleanor@argotpartners.com
Media:
David Rosen, 212-600-1902
david.rosen@argotpartners.com
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