ROCKVILLE, Md., May 14, 2021 /PRNewswire/ --
- RGX-121, a one-time gene therapy for MPS II, continues to be
well-tolerated with no drug-related serious adverse events
- Biomarkers and measures of neurodevelopmental function from
patients in Cohorts 1 and 2 continue to indicate CNS activity
following RGX-121 administration
- Evidence of systemic enzyme expression and biomarker
activity continues to be observed
- REGENXBIO recently initiated dosing of patients in Cohort
3
REGENXBIO Inc. (Nasdaq: RGNX) today announced a safety update
and additional positive interim data from the ongoing Phase I/II
trial of RGX-121 for the treatment of patients up to 5 years old
diagnosed with Mucopolysaccharidosis Type II (MPS II), also known
as Hunter Syndrome. The latest data from this trial will be
presented today at the American Society of Gene and Cell Therapy
(ASGCT) 24th Annual Meeting by Dr. Roberto Giugliani,
Professor, Department of Genetics, UFRGS, Medical Genetics Service,
HCPA, Porto Alegre, Brazil.
"I am pleased to report additional data from the Phase I/II
trial of RGX-121 in patients with MPS II. The biomarker data from
these patients continues to demonstrate that the I2S enzyme is
active in the CNS and importantly, continued cognitive development
has been observed in the majority of patients who have been
followed for more than 6 months. In addition, emerging evidence of
systemic enzyme expression and activity has been shown in urine and
plasma, including in patients who are naive to enzyme replacement
therapy, the current standard of care," said Dr. Giugliani. "The
potential to provide therapeutic benefit from a one-time gene
therapy would be a meaningful advancement for the treatment of MPS
II patients."
"It is encouraging to see continued efficacy signals up to two
years after administration of RGX-121 in our Phase I/II trial. The
safety profile we have seen to date, combined with evidence of CNS
and systemic effects, are encouraging as we seek to bring a
one-time gene therapy treatment to the MPS II community," said
Steve Pakola, M.D., Chief Medical
Officer of REGENXBIO. "We have begun dosing patients in Cohort 3,
and we look forward to providing further program updates later this
year."
RGX-121 is an investigational one-time gene therapy designed to
deliver the gene that encodes the iduronate-2-sulfatase (I2S)
enzyme using the AAV9 vector. RGX-121 is administered directly to
the central nervous system (CNS). Patients in Cohorts 1 and 2
received doses of RGX-121 at 1.3x1010 genome copies per
gram (GC/g) of brain mass and 6.5x1010 GC/g of brain
mass, respectively. REGENXBIO began dosing patients in Cohort 3 at
an increased dose of 2.0x1011 GC/g of brain mass. As of
April 25, 2021, RGX-121 is reported
to be well-tolerated with no drug-related serious adverse events
(SAEs) in nine patients dosed with RGX-121 in Cohorts 1-3.
Data Summary and Safety Update from Cohort 1 and 2
Time of post-administration follow-up for patients in Cohorts 1
and 2 ranges from 24 weeks to two years. Five patients have
completed the 48-week immunosuppression regimen, per study
protocol. Six of the patients were receiving weekly, intravenous
enzyme replacement therapy (ERT) at the time of enrollment; two of
these patients have since discontinued ERT.
CSF Biomarker Data from Cohort 1 and 2
Biomarker data from patients in Cohorts 1 and 2 indicate
encouraging signals of I2S enzyme activity in the CNS following
one-time administration of RGX-121. Heparan sulfate (HS) levels are
a key biomarker of I2S enzyme activity and the patients in Cohorts
1 and 2 demonstrated decreased HS in the cerebrospinal fluid (CSF)
up to 2 years following RGX-121 administration. Combined median
reductions from baseline were 30.3% at Week 8 and 35.0% at the last
timepoint available for each patient. Similarly, these patients
demonstrated decreased levels of D2S6, a component of HS, up to 2
years following RGX-121 administration, with median reductions from
baseline of 44.1% at Week 8 and 40.4% at the last timepoint
available for each patient. In addition, I2S enzyme concentration
in the CSF, which was undetectable in all patients prior to dosing,
was measurable in all five patients from Cohort 2 after RGX-121
administration.
Neurocognitive Development Data from Cohort 1 and 2
Patients in Cohorts 1 and 2 also demonstrated continued
neurocognitive development up to two years after RGX-121
administration. Five patients have assessments of neurodevelopment
function at timepoints beyond 6 months, and of those patients, four
have continued to demonstrate neurocognitive development, according
to the Bayley Scales1. One patient entered the study
with significant delay in neurocognitive development at baseline
but has demonstrated relative stabilization following RGX-121
administration and has continued to acquire expressive and
receptive language skills based on the Bayley Scales.
Systemic Biomarker Data and Clinical Efficacy
Patients in Cohorts 1 and 2 demonstrated evidence of I2S enzyme
activity in urine following administration of RGX-121. Notably, two
patients in Cohort 2 who were naive to ERT demonstrated rapid
reductions in urine total glycosaminoglycans (GAG) levels of over
50% at the latest timepoint available following RGX-121
administration. Two patients in Cohort 1 discontinued ERT over one
year after administration of RGX-121, and the total urine GAG
levels following ERT withdrawal remained relatively consistent with
total urine GAG levels prior to ERT withdrawal. Total urine GAG
levels decreased among four patients who continue to receive ERT
following administration of RGX-121. Patients in both cohorts
demonstrated increases in I2S protein concentration levels in
plasma over time following administration of RGX-121.
The study findings are available
at https://www.asgct.org.
About RGX-121
RGX-121 is a product candidate for the treatment of
Mucopolysaccharidosis Type II (MPS II), also known as Hunter
Syndrome. RGX-121 is designed to use the AAV9 vector to deliver the
human iduronate-2-sulfatase gene (IDS) which encodes the
iduronate-2-sulfatase (I2S) enzyme to the central nervous system
(CNS). Delivery of the IDS gene within cells in the CNS
could provide a permanent source of secreted I2S beyond the
blood-brain barrier, allowing for long-term cross correction of
cells throughout the CNS. RGX-121 has received orphan drug product,
rare pediatric disease and Fast Track designations from the U.S.
Food and Drug Administration.
About Mucopolysaccharidosis Type II (MPS II)
MPS II, or Hunter Syndrome, is a rare, X-linked recessive
disease caused by a deficiency in the lysosomal enzyme
iduronate-2-sulfatase (I2S) leading to an accumulation of
glycosaminoglycans (GAG), including heparan sulfate (HS) in tissues
which ultimately results in cell, tissue, and organ dysfunction. In
severe forms of the disease, early developmental milestones may be
met, but developmental delay is readily apparent by 18 to 24
months. Specific treatment to address the neurological
manifestations of MPS II and prevent or stabilize cognitive decline
remains a significant unmet medical need. Key biomarkers of I2S
enzymatic activity in MPS II 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 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," "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, 2020 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:
Tricia Truehart
Investor Relations and Corporate Communications
347-926-7709
ttruehart@regenxbio.com
Investors:
Brendan Burns, 212-600-1902
brendan@argotpartners.com
Media:
David Rosen, 212-600-1902
david.rosen@argotpartners.com
1 Bayley Scales of Infant and Toddler
Development, 3rd Edition (BSID-III)
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