ROCKVILLE, Md., Dec. 18,
2019 /PRNewswire/ -- REGENXBIO Inc. (Nasdaq: RGNX), a leading
clinical-stage biotechnology company seeking to improve lives
through the curative potential of gene therapy based on its
proprietary NAV® Technology Platform, today
announced interim data from the first cohort of the ongoing Phase
I/II trial of RGX-121 for the treatment of Mucopolysaccharidosis
Type II (MPS II), also known as Hunter syndrome. RGX-121 is an
investigational one-time gene therapy designed to deliver the gene
that encodes the iduronate-2-sulfatase (I2S) enzyme direct to the
central nervous system (CNS) using the AAV9 vector.
"Patients with MPS II continue to have significant difficulties
despite the availability of systemic enzyme replacement therapy
which doesn't address manifestations of the disease in the central
nervous system such as impaired cognitive development. We are
pleased with the emerging safety profile in the first patients
dosed with RGX-121 via single intracisternal administration. We are
also encouraged by the positive results from this cohort, including
a meaningful and sustained reduction in heparan sulfate suggesting
that the gene therapy can potentially restore intracellular
activity of the I2S enzyme, as well as the early signs of
neurocognitive stability that have been observed," said
Steve Pakola, M.D., Chief Medical
Officer of REGENXBIO. "Based on the data from these patients, we
have advanced the study into a second cohort of patients at an
increased dose level, and look forward to expanding the RGX-121
clinical program in order to bring this novel therapy to patients
as quickly as possible."
In Cohort 1 of the Phase I/II study, three patients were dosed
intracisternally at the ages of 5 months (Patient 1), 35 months
(Patient 2), and 7 months (Patient 3) with 1.3x1010
genome copies per gram (GC/g) of brain mass. Safety follow-up
post-administration of RGX-121 ranges from 12 weeks to 68 weeks. As
of December 16, 2019, RGX-121 is
reported to be well-tolerated, with no drug-related serious adverse
events (SAEs) reported. Two SAEs were reported and are not
considered to be related to the gene therapy or the administration
of RGX-121. Per protocol, patients received a 48 week
immunosuppression regimen to minimize the potential for
immune-mediated reactions and importantly, Patient 1 has completed
the immunosuppression regimen.
Heparan sulfate (HS) is a key biomarker of I2S enzyme activity
and is being measured in the cerebral spinal fluid (CSF) following
administration of RGX-121. In MPS II patients, high amounts of HS
accumulate in the CNS, closely correlating with neurocognitive
decline. In the CSF of all three patients enrolled in Cohort 1, HS
levels demonstrated a mean reduction of 33.3% from baseline to Week
8. Patient 1 demonstrated consistent decreases in HS levels in the
CSF over time, with a 27.4% reduction from baseline at Week 8 and a
43.6% reduction from baseline at Week 48, the latest timepoint
available. Patient 2 also demonstrated a decrease of HS levels in
the CSF, with a 30.9% reduction from baseline to Week 8, the latest
timepoint available. Patient 3 demonstrated a decrease in HS levels
in the CSF with a reduction of 41.6% from baseline to Week 8, the
latest timepoint available.
In addition, for the two patients who have progressed beyond
Week 24, preliminary data indicates stability of neurocognitive
development. Patient 1 has continued to exhibit normal cognitive
development as expected at Week 48, the time of last assessment.
Patient 2 was diagnosed with a neurocognitive decline prior to
dosing with RGX-121 and remains developmentally delayed, but
preliminary assessments suggest stable neurocognitive development
since dosing.
"It is encouraging to see a reduction in heparan sulfate in the
CSF as it is a strong marker of the decline in neurocognitive
development experienced by patients with MPS II, and closely
correlates with the severity of the disease. The potential to
provide therapeutic benefit directly to the CNS would be a
meaningful advancement for the treatment of MPS II patients,"
commented Barbara Burton, M.D.,
Professor of Pediatrics at the Northwestern
University Feinberg School of Medicine and pediatric
geneticist at Ann & Robert H. Lurie Children's Hospital of
Chicago.
Additional data will be presented at an upcoming medical
conference in early 2020.
Following review of the safety and efficacy data from all three
patients in Cohort 1, the Independent Data Monitoring Committee for
the Phase I/II study of RGX-121 approved the continuation and dose
escalation into Cohort 2. Subsequently, RGX-121 was administered to
the first patient in Cohort 2 at a dose of 6.5x1010 GC/g
of brain mass. Clinical sites are active and recruiting patients,
including University of Pittsburgh
School of Medicine, Children's Hospital of Philadelphia and UCSF Benioff Children's
Hospital Oakland in the United
States, and Hospital de Clínicas de Porto Alegre in Brazil.
"We are pleased that this program is continuing to advance as a
potential CNS-specific treatment option for MPS II patients," said
Terri Klein, President and Chief
Executive Officer of the National MPS Society. "We appreciate
REGENXBIO's dedication to the MPS community and look forward to
additional development updates."
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 (IDS) gene 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 the Phase I/II Clinical Trial of RGX-121
RGX‑121 is being evaluated in a Phase I/II, multi-center,
open-label, multiple-cohort, dose‑escalation study in patients with
Mucopolysaccharidosis Type II (MPS II) in the United States and Brazil. The Phase I/II trial is designed to
evaluate the safety of RGX-121 in up to 6 patients less than five
years of age who have or are at high risk of developing
neurocognitive effects. In addition, the study will evaluate the
effect of RGX-121 on biomarkers of iduronate-2-sulfatase (I2S)
enzyme activity as well as neurocognitive deficits and other
clinical measures.
About Mucopolysaccharidosis Type II (MPS II)
MPS II 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, 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," "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 Phase I/II trial of
RGX-121 for the treatment of MPS II. 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, 2018, 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. 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:
Heather Savelle, 212-600-1902
heather@argotpartners.com
Media:
David Rosen, 212-600-1902
david.rosen@argotpartners.com
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