- RGX-202, a potential one-time AAV Therapeutic for the
treatment of Duchenne that includes an optimized transgene for a
novel microdystrophin, continues to be well-tolerated in three
patients from dose level 1 (1x1014 GC/kg)
- Initial biomarker data in two patients who completed
three-month assessment demonstrate robust microdystrophin
expression with localization to the muscle cell membrane
- Patient aged 4.4 years old had expression level at 38.8% of
control
- Trial dose escalation expected by end of 2023
- Pivotal dose determination and initiation of pivotal program
anticipated in 2024
- Plan to use RGX-202 microdystrophin as a surrogate endpoint
to support a Biologics License Application filing using the
accelerated approval pathway
- RGX-202 development program uses commercial-ready cGMP
material from the REGENXBIO Manufacturing Innovation
Center
- Conference call today, Tuesday,
October 3, 2023, at 4:30 p.m.
ET
ROCKVILLE, Md., Oct. 3, 2023
/PRNewswire/ -- REGENXBIO Inc. (Nasdaq: RGNX) today announced
additional interim safety data and initial efficacy data from the
Phase I/II AFFINITY DUCHENNE™ trial of RGX-202 for the treatment of
Duchenne Muscular Dystrophy (Duchenne). Results were shared at the
28th Annual International Congress of the World Muscle
Society.
"Duchenne is a rare degenerative disease, and without a
functional dystrophin protein, muscles progressively weaken,
leading to loss of mobility and declining respiratory and cardiac
function," said Olivier Danos,
Ph.D., Chief Scientific Officer of REGENXBIO. "The unique construct
of RGX-202, inclusive of the C-Terminal domain, has the potential
to make a meaningful impact for patients and we are encouraged by
these interim safety and efficacy results."
RGX-202 is an investigational one-time AAV therapeutic for
Duchenne, using the NAV® AAV8 vector to deliver a
transgene for a novel microdystrophin that includes the functional
elements of the C-Terminal (CT) domain as well as a muscle-specific
promoter to support a targeted therapy for improved resistance to
muscle damage associated with Duchenne.
Data were presented from dose level 1 (1x1014 genome
copies (GC)/kg body weight) of the ongoing Phase I/II AFFINITY
DUCHENNE™ trial, which continues to recruit ambulatory patients
(aged 4 to 11 years) and is using commercial-ready cGMP material
from the REGENXBIO Manufacturing Innovation Center.
Safety Update
As of September
28, 2023, RGX-202 was reported to be well tolerated with no
drug-related serious adverse events in three patients, aged 4.4,
10.6 and 6.3 years, dosed to date at dose level 1. Time of
post-administration follow up ranges from three weeks to more than
five months. The two patients who reached three-month follow-up
have completed the immunosuppression regimen per study
protocol.
Biomarker Data
Initial biomarker data from two
patients who completed three-month trial assessments indicate
encouraging increases in expression of RGX-202 microdystrophin from
bicep muscle biopsies taken at three months following one-time
administration of RGX-202. In addition, RGX-202 microdystrophin was
detectable by immunofluorescence staining throughout muscle tissue
at three months, with RGX-202 microdystrophin protein localized to
the sarcolemma.
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.
In the patient aged 4.4 years old, RGX-202 microdystrophin
expression was measured to be 38.8% compared to control. A
reduction from baseline in serum creatinine kinase (CK) levels of
43% was observed at ten weeks, supporting evidence of clinical
improvement. Elevated CK levels are associated with muscle injury
and are uniformly elevated in patients with Duchenne.
In the patient aged 10.6 years old, RGX-202 microdystrophin
expression was measured to be 11.1% compared to control and a
reduction from baseline in serum CK levels of 44% was observed at
ten weeks.
"I am encouraged by these initial results demonstrating that
RGX-202 appears to be well tolerated and leads to robust
microdystrophin expression in muscle tissue, which are important
early findings," said Aravindhan Veerapandiyan, M.D., Pediatric
Neuromuscular Neurologist, Arkansas Children's Hospital, and
primary investigator in the trial. "I know that there is still
unmet need for these boys for new treatment options that have the
potential to impact the trajectory of the disease."
Clinical Program Updates
REGENXBIO expects to dose
patients at dose level 2 (2x1014 genome copies (GC)/kg
body weight) in the Phase I/II AFFINITY DUCHENNE trial by the end
of 2023. In addition, the trial protocol has been amended to
accelerate the development of RGX-202, updating the dose expansion
phase of the trial to begin after two patients, from the previous
three patients.
Today, REGENXBIO also provided an update on a newly completed
preclinical efficacy study evaluating RGX-202 manufactured using
REGENXBIO's NAVXpress™ commercial-ready process at both dose
levels. RGX-202 at dose level 2 showed improvement in functional
performance, compared to dose level 1, as determined by forelimb
muscle strength and treadmill exhaustion in mdx mice. This
data further supports plans to immediately initiate dose escalation
to dose level 2.
The Company expects to share initial strength and functional
assessment data for both dose levels in 2024. Additionally,
REGENXBIO expects to make a pivotal dose determination and initiate
a pivotal program for RGX-202 in 2024.
"We are pleased to share these encouraging results and updates,
enabling us to accelerate our development of RGX-202 with the goal
of reaching pivotal phase faster," said Kenneth T. Mills, President and Chief Executive
Officer of REGENXBIO. "We plan to scale up production of RGX-202
using commercial-ready cGMP material from the REGENXBIO
Manufacturing Innovation Center to support a pivotal program in
2024, with a clear path to submit a BLA using the accelerated
approval pathway, with RGX-202 microdystrophin as a surrogate
endpoint for clinical benefit. This update firmly establishes
RGX-202 as a key feature of our '5x'25' vision to have five gene
therapies either on the market or in late-stage development by
2025."
Conference Call Details
REGENXBIO will host a
conference call Tuesday, October 3 at
4:30 p.m. ET with principal
investigator, Dr. Aravindhan Veerapandiyan, to discuss these
results and the RGX-202 program.
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 genome copies (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 up to seven additional patients to be enrolled at
each dose level (for a total of up to nine patients in each dose
cohort).
The trial design consists of thorough safety measures 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.
Initial trial sites are located in the U.S., with additional sites
in Canada and Europe expected to follow.
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, 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, 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
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