- Completed enrollment in cohort 2 of the Phase I/II AFFINITY
DUCHENNE® trial of RGX-202, a potential one-time AAV
Therapeutic for the treatment of Duchenne that includes an
optimized transgene for a novel microdystrophin
- New three-month assessment in third patient at dose level 1
demonstrates largest increase in microdystrophin expression
- Patient aged 6.6 years old had expression level at 83.4% of
control
- On track to initiate pivotal trial in second half of
2024
- Company plans to discuss these new results as part of a full
rare disease program update on its conference call today,
Wednesday, February 7, 4:30 p.m. ET
ROCKVILLE, Md., Feb. 7, 2024
/PRNewswire/ -- REGENXBIO Inc. (Nasdaq: RGNX) today
announced that enrollment has completed at dose level 2 and
reported additional interim safety and efficacy in the Phase I/II
AFFINITY DUCHENNE® trial of RGX-202 in patients
with Duchenne muscular dystrophy (Duchenne) ages 4 to11 years
old.
"We are thrilled to see that RGX-202 is demonstrating strong
microdystrophin expression across a wide range of patients," said
Kenneth T. Mills, President and CEO,
REGENXBIO. "RGX-202 microdystrophin is differentiated with
important biology most similar to naturally occurring dystrophin
that protects from the muscle degradation associated with Duchenne.
All boys with Duchenne are in need of new treatment options that
can meaningfully impact disease, and we are working with great
urgency to accelerate RGX-202 as an option for them."
Safety Update
As of February 6,
2024, RGX-202 has been well tolerated with no drug-related
serious adverse events in five patients, aged 4.4 to 12.1 at dose
level 1 (1x1014 genome copies (GC)/kg body weight)
and dose level 2 (2x1014 GC/kg body weight). Time
of post-administration follow up ranges from approximately three
weeks to over nine months. All patients who reached three-month
follow-up have completed the immunosuppression regimen per study
protocol.
Biomarker Data
In new data from the third patient,
aged 6.6 years, who received RGX-202 at dose level 1, RGX-202
microdystrophin expression was measured to be 83.4% compared to
control at three months. A reduction from baseline in serum
creatinine kinase (CK) levels of 93% was observed at ten weeks.
All three patients, at dose level 1, who completed three-month
trial assessments indicate encouraging increases in expression of
RGX-202 microdystrophin and reduction from baseline in serum CK
levels, supporting evidence of clinical improvement.
RGX-202 microdystrophin levels were measured using an automated
and precise western blot method (Jess), and comparable results were
confirmed with a proprietary liquid chromatography-mass
spectrometry (LC-MS) method. Elevated CK levels are associated with
muscle injury and are uniformly elevated in patients with Duchenne.
The mean (SD) RGX-202 microdsytrophin expression levels (change
from baseline) at three months following RGX-202 administration
were 44.4% (n=3, SD:36.5%). The patient data is presented
below.
Patient
|
Age at
Dosing (years)
|
Weight at
Dosing (kg)
|
Western blot (Jess
method),
RGX-202
Microdystrophin
(% Normal
Control)
|
CK Levels,
week 10 (% reduction
from baseline)
|
1
|
4.4
|
17.8
|
38.8
|
-43
|
2
|
10.5
|
28.3
|
11.1
|
-44
|
3
|
6.6
|
26.8
|
83.4
|
-93
|
Clinical Program Updates
REGENXIO expects to make a
pivotal dose determination in mid-2024. The Company also expects to
share initial strength and functional assessment data for both dose
levels and the initiation of a pivotal trial in the second half of
2024. The Company plans to use RGX-202 microdystrophin expression
as a surrogate endpoint to support a Biologics License Application
(BLA) filing using the accelerated approval pathway.
"On our call this afternoon, we look forward to discussing these
new clinical results and also reaffirming our guidance for the
submission of a BLA this year for RGX-121 for the treatment of MPS
II. The exciting topline pivotal data supporting this submission
will be released later this morning in conjunction with a
presentation at the 20th Annual WORLDSymposium™," said
Mills.
Conference Call Details
REGENXBIO will host a
conference call Wednesday, February 7
at 4:30 p.m. ET. Listeners can
register for the webcast via this link. Analysts wishing to
participate in the question and answer session should use
this link. A copy of the slides being presented will be
available via the Company's investor website. Those who plan on
participating are advised to join 15 minutes prior to the start
time. A replay of the webcast will also be available via the
Company's investor website approximately two hours after the call's
conclusion.
AFFINITY DUCHENNE Trial Design
The Phase I/II AFFINITY
DUCHENNE trial is a multicenter, open-label dose escalation and
dose expansion clinical study to evaluate the safety, tolerability
and clinical efficacy of a one-time intravenous (IV) dose of
RGX-202 in patients with Duchenne. In the dose evaluation phase of
the trial, four ambulatory, pediatric patients (ages 4 to 11 years
old) are expected to enroll in two cohorts with doses of
1x1014 GC/kg body weight (n=2) and
2x1014 GC/kg body weight (n=2). After an
independent safety data review for each cohort, a dose expansion
phase of the trial may allow for additional patients to be
enrolled.
The trial design was informed by the Duchenne community and
engagement with key opinion leaders, including a comprehensive,
short-term, prophylactic immunosuppression regimen to proactively
mitigate potential complement-mediated immunologic responses, and
inclusion criteria based on dystrophin gene mutation status,
including DMD gene mutations in exons 18 and above. Trial endpoints
include safety, immunogenicity assessments, pharmacodynamic and
pharmacokinetic measures of RGX-202, including microdystrophin
protein levels in muscle, and strength and functional assessments,
including the North Star Ambulatory Assessment (NSAA) and timed
function tests.
About RGX-202
RGX-202 is designed to deliver a
transgene for a novel microdystrophin that includes the functional
elements of the C-Terminal (CT) domain found in naturally occurring
dystrophin. Presence of the CT domain has been shown in preclinical
studies 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 support the delivery and targeted expression of genes
throughout skeletal and heart muscle using the NAV AAV8 vector, a
vector used in numerous clinical trials, and a well-characterized
muscle-specific promoter (Spc5-12).
About Duchenne Muscular Dystrophy
Duchenne is a
severe, progressive, degenerative muscle disease, affecting 1 in
3,500 to 5,000 boys born each year worldwide. Duchenne is caused by
mutations in the Duchenne 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.
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 and AAV9. REGENXBIO and
its third-party NAV Technology Platform Licensees are applying the
NAV Technology Platform in the development of a broad pipeline of
candidates, including late-stage and commercial programs, in
multiple therapeutic areas. REGENXBIO is committed to a "5x'25"
strategy to progress five AAV Therapeutics from our internal
pipeline and licensed programs into pivotal-stage or commercial
products by 2025.
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," "assume," "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, clinical trials, costs
and cash flow. 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, 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, 2022, 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. Except as required by law,
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:
Dana
Cormack
Corporate Communications
dcormack@regenxbio.com
Investors:
Chris Brinzey
ICR Westwicke
339-970-2843
chris.brinzey@westwicke.com
View original content to download
multimedia:https://www.prnewswire.com/news-releases/regenxbio-announces-completion-of-enrollment-in-cohort-2-and-additional-positive-interim-data-in-affinity-duchenne-trial-302055713.html
SOURCE REGENXBIO Inc.