- New three-month assessment in first patient at dose level 2
demonstrates robust microdystrophin expression
- Patient aged 12 years at dosing had expression level at
75.7% of control
- Early evidence of strength and motor function improvement
observed
- On track to initiate pivotal trial in second half of
2024
- Webcast this morning, Tuesday, March
5, 8:30 a.m. ET, with
principal investigator
ROCKVILLE, Md., March 5,
2024 /PRNewswire/ -- REGENXBIO Inc. (Nasdaq:
RGNX) today reported additional interim safety and efficacy
data in the Phase I/II AFFINITY DUCHENNE® trial of
RGX-202 in patients with Duchenne muscular dystrophy (Duchenne)
ages 4 to11 years old, including RGX-202 microdystrophin expression
from dose level 2 and video of trial clinic assessments
demonstrating initial evidence of strength and functional
improvement.
"RGX-202 at dose level 2 is demonstrating significantly
increased microdystrophin expression in a 12-year-old patient,"
said Kenneth T. Mills, President and
CEO, REGENXBIO. "We know there is an insufficient level of data
available to the community for boys older than 7 years, and we are
committed to being transparent with our data for a Duchenne
community in need of new treatment options that can meaningfully
impact disease. In addition, we are encouraged by the safety data
at both dose levels and initial caregiver observations of strength
and motor function improvement in boys treated with RGX-202. We
look forward to following these patients to establish durability
and greater separation from baseline, which we hope will further
establish RGX-202 as an important option among treatments in
development."
"There is a need for treatment options for boys with Duchenne
that have the potential to alter the disease trajectory," said
Aravindhan Veerapandiyan, M.D., Arkansas Children's Hospital. "I am
very pleased with the new microdystrophin expression data from
RGX-202 dose level 2. It is encouraging to see that patients are
safely progressing through their trial protocol strength and motor
function assessments with early observations of improvement,
including in older boys."
Safety Update
As of February
28, 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 seven weeks to over eleven months. All patients who
reached three-month follow-up have completed the immunosuppression
regimen per study protocol.
Biomarker Data and Recorded Strength and Functional
Observations
In new data from the first patient, aged 12.1
years, who received RGX-202 at dose level 2, RGX-202
microdystrophin expression was measured to be 75.7% compared to
control at three months. A reduction from baseline in serum
creatinine kinase (CK) levels of 77% was observed at ten weeks.
All four patients, across both dose levels, 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.
Among patients aged 8 to 11 years old at screening, RGX-202
microdsytrophin expression levels (change from baseline) at three
months following RGX-202 administration was higher in dose level 2.
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)
|
Dose level
1
|
1
|
4.4
|
17.8
|
38.8
|
-43
|
2
|
10.5
|
28.3
|
11.1
|
-44
|
3
|
6.6
|
26.8
|
83.4
|
-93
|
Dose level
2
|
4
|
12.1
|
24.3
|
75.7
|
-77
|
Dose Comparison of RGX-202 Microdystrophin Expression Levels
in Older Boys
|
Dose level
1
|
Dose level
2
|
Ages > 8
years
|
11.1
|
75.7
|
In addition, new recordings of the AFFINITY DUCHENNE trial
clinic assessments and home videos shared with trial investigators
by caregivers illustrate patients treated with RGX-202 are
demonstrating initial evidence of strength and functional
improvement.
"Several of the items in the clinic recordings are timed tasks
and they are also measured on the NSAA. We plan to present strength
and functional assessment data for both dose levels from the trial
later this year, but today this is a glimpse of how these boys are
gaining functional skills since dosing," said Dr. Veerapandiyan,
"The montage of home videos provides some insight into a family's
experience with RGX-202. Being able to do these activities, which
can be quite difficult for boys with Duchenne, is informal, but a
set of important observations of their experience."
Clinical Program Updates
REGENXBIO expects to make a
pivotal dose determination in mid-2024. The Company also expects to
share 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.
Conference Call Details
REGENXBIO will host a webcast
Tuesday, March 5 at 8:30 a.m. ET. The live webcast can be accessed in
the Investors section of REGENXBIO's website
at www.regenxbio.com. An archived replay of the webcast will
be available for approximately 30 days following the
presentation.
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 has differentiated and important
biology most similar to naturally occurring dystrophin that
protects from the muscle degradation associated with Duchenne.
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. Since its founding
in 2009, REGENXBIO has pioneered the development of AAV
Therapeutics, an innovative class of gene therapy medicines.
REGENXBIO is advancing a pipeline of AAV Therapeutics for retinal
and rare diseases, including ABBV-RGX-314 for the treatment of wet
AMD and diabetic retinopathy, being developed in collaboration with
AbbVie, RGX-202 for the treatment of Duchenne and RGX-121 for the
treatment of MPS II. Thousands of patients have been treated with
REGENXBIO's AAV Therapeutic platform, including Novartis' ZOLGENSMA
for children with spinal muscular atrophy. Designed to be one-time
treatments, AAV Therapeutics have the potential to change the way
healthcare is delivered for millions of people. For more
information, please visit www.regenxbio.com.
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, 2023, 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.
Zolgensma® is a registered trademark of Novartis Gene
Therapies. All other trademarks referenced herein are registered
trademarks of REGENXBIO.
Contacts:
Dana
Cormack
Corporate Communications
dcormack@regenxbio.com
Investors:
Chris Brinzey
ICR Westwicke
339-970-2843
chris.brinzey@westwicke.com
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