- RGX-111 is an investigational AAV Therapeutic for the
treatment of severe MPS I that is part of REGENXBIO's
clinical-stage pipeline of neurodegenerative disease
programs
-
- RGX-111, a potential one-time gene therapy for MPS I,
continues to be well-tolerated across two dose levels, with no
drug-related serious adverse events
- New biomarker and neurodevelopmental data continue to
indicate encouraging CNS profile in patients dosed with
RGX-111
- Company is on track to manufacture commercial-scale cGMP
material to support the continued development of RGX-111
ROCKVILLE, Md., Feb. 24,
2023 /PRNewswire/ -- REGENXBIO Inc. (Nasdaq:
RGNX) today announced positive interim data from the Phase I/II
trial of RGX-111 for the treatment of severe Mucopolysaccharidosis
Type I (MPS I). Data from the Phase I/II trial and single-patient
Investigational New Drug (IND) application of RGX-111 were
presented by Ray Wang, M.D.,
Campbell Foundation Director of the Multidisciplinary Lysosomal
Program, Division of Metabolic Disorders, CHOC Children's Hospital,
Department of Pediatrics, University of
California, Irvine, at the 19th Annual
WORLDSymposium™.
"RGX-111 is our second-most advanced clinical candidate in our
neurodegenerative disease pipeline and is part of our '5x'25'
strategy to have five gene therapies either on the market or in
late-stage development by 2025. We are encouraged to see that this
potential one-time gene therapy using our NAV AAV9 vector continues
to demonstrate compelling evidence of CNS biomarker activity," said
Kenneth T. Mills, President and
Chief Executive Officer of REGENXBIO. "In connecting with MPS I
families, we understand the need for new treatment options that can
impact daily living, and we're pleased to see that most patients in
this trial demonstrated continued skill acquisition across multiple
neurodevelopmental assessments."
"There is a great need for new treatment options that provide
lasting expression of the IDUA enzyme and the reduction of
glycosaminoglycans in the central nervous system," said Dr.
Wang. "I am encouraged by the emerging clinical profile of
RGX-111 based on this data, including the important
neurodevelopment gains in cognition, language, fine motor skills
and personal and social skills for daily living."
RGX-111 is an investigational one-time gene therapy designed to
deliver the gene that encodes the IDUA enzyme using the AAV9
vector. RGX-111 is administered directly to the central nervous
system (CNS). The primary endpoint of the trial is to evaluate the
safety of RGX-111. Secondary and exploratory endpoints include
biomarkers of IDUA enzyme activity in the cerebrospinal fluid
(CSF), serum and urine, neurodevelopmental assessments, and
caregiver reported outcomes. Patients were treated across two dose
cohorts: 1.0x1010 genome copies per gram (GC/g) of brain
mass (n=2) and 5.0x1010 GC/g of brain mass (n=6). In the
single-patient IND for RGX-111, a severe MPS I patient was dosed
with 1x1010 GC/g of brain mass.
REGENXBIO plans to continue having early and frequent
communication with regulatory agencies about pathways to expedite
the development of its neurodegenerative disease pipeline. In the
first half of 2023, REGENXBIO expects to use its Manufacturing
Innovation Center to produce RGX-111 commercial-scale cGMP material
from its proprietary, high-yielding suspension-based manufacturing
process, named NAVXPress™.
Data Summary and Safety Data
As of January 17, 2023, RGX-111 was reported to be well
tolerated in the eight patients enrolled in the Phase I/II clinical
trial with no drug-related serious adverse events (SAEs). Time of
post-administration follow-up ranged from seven to 103 weeks. Two
patients in Cohort 1 and three patients in Cohort 2 have completed
the 48-week immunosuppression regimen, per the study protocol.
RGX-111 continued to be well-tolerated in the single-patient IND
with no drug-related SAEs as of December 12,
2021. Time of post-administration follow-up was 87 weeks.
This patient has completed the 48-week immunosuppression regimen,
per the study protocol, and continues to receive weekly ERT.
CSF Biomarker Data
Data from patients in the Phase
I/II trial and the single-patient IND indicate positive IDUA
biomarker activity in the CNS following one-time administration of
RGX-111. Heparan sulfate (HS) is a glycosaminoglycan (GAG) that is
a key biomarker of IDUA enzyme activity. In the Phase I/II trial, a
decrease in CSF HS was observed through the last timepoint
available in the majority of patients following administration of
RGX-111. Measurable CSF IDUA enzyme activity was detected after
RGX-111 administration in four of the five Phase I/II trial
patients and in the single patient IND participant.
Neurodevelopmental Data
Patients in the Phase I/II
trial and the single-patient IND demonstrated encouraging continued
neurodevelopmental skill acquisition, as measured by age and
developmentally appropriate validated instruments for
neurodevelopmental testing, including the Bayley Scales of
Infant Development (BSID-III) for chronological or developmental
ages 0-42 months, Wechsler Abbreviated Scale of Intelligence
(WASI-II) for chronological and developmental age greater than six
years, and the Vineland Adaptive Behavior Scale (VABS-III; across
all age groups).
All five patients assessed with BSID-III demonstrated continued
developmental skill acquisition on all subsets (cognition,
expressive language and fine motor). At the last assessment, four
of the five patients had function ≥ -2 standard deviations of the
normative mean on the cognition, expressive language and fine motor
subtests. Cognitive function in a Phase I/II trial patient and the
single IND patient was higher than the age equivalent scores in the
available natural history data.
One patient in Cohort 1 who entered the trial at 13 years old
demonstrated neurodevelopmental improvements as measured by the
WASI-II and showed improvement in the majority of subdomains of the
VABS-III at approximately 18 months after RGX-111
administration.
Systemic Biomarker Data
Evidence of systemic
biomarker activity was observed in patients in both cohorts of the
Phase I/II trial and the single-patient IND. Patients who had
elevated baseline levels of I0S6 in plasma, a key biomarker of IDUA
enzyme activity in MPS I patients, demonstrated decreases in I0S6
levels following administration of RGX-111. In addition, the
majority patients dosed with RGX-111 maintained low levels of total
urine GAGs at the last timepoint available.
The study findings presented at the WORLDSymposium are
available under the Presentations & Publications page in the
Media section of the company's website, located at
www.regenxbio.com.
About RGX-111
RGX-111 is designed to use the AAV9
vector to deliver the α-l-iduronidase (IDUA) gene to the central
nervous system (CNS). Delivery of the IDUA gene within the cells in
the central nervous system (CNS) could provide a permanent source
of secreted IDUA beyond the blood-brain barrier, allowing for
long-term cross-correction of cells throughout the CNS. By
providing rapid IDUA delivery to the brain, RGX-111 could
potentially help prevent the progression of cognitive deficits that
otherwise occurs in MPS I patients. RGX-111 has received orphan
drug product, rare pediatric disease and Fast Track designations
from the U.S. Food and Drug Administration.
About Mucopolysaccharidosis Type I (MPS I)
MPS I is a
rare autosomal recessive genetic disease caused by a deficiency in
the lysosomal enzyme alpha-L-iduronidase (IDUA), leading to an
accumulation of glycosaminoglycans (GAGs) including heparan sulfate
(HS) in tissues which ultimately results in cell, tissue, and organ
dysfunction, including in the central nervous system (CNS). This
can include excessive accumulation of fluid in the brain, spinal
cord compression, and cognitive impairment. MPS I is estimated to
occur in 1 in 100,000 births. Current disease modifying therapies
for MPS I include hematopoietic stem cell transplant (HSCT) and
enzyme replacement therapy with a recombinant form of human IDUA
administered intravenously. However, intravenous enzyme therapy
does not treat the CNS manifestations of MPS I, and HSCT can be
associated with clinically significant morbidity and mortality. Key
biomarkers of IDUA enzymatic activity in MPS I patients include its
substrate heparan sulfate (HS), which has been shown to correlate
with neurocognitive manifestations of the disorder.
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 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, 2021, 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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