ROCKVILLE, Md., Dec. 8, 2020 /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 Cohorts 1 and 2 of 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). In addition, REGENXBIO announced plans to evaluate a higher
dose of RGX-121 in a third cohort of patients at an increased dose
of 2.0x1011 GC/g brain mass. REGENXBIO expects to begin
enrolling patients in Cohort 3 in the first quarter of 2021.
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 delivered directly to the
central nervous system (CNS) via intracisternal administration.
"We are very pleased to see the encouraging safety profile of
RGX-121, as well as additional evidence of long-term biomarker
activity and neurocognitive development in patients with MPS II up
to two years after RGX-121 administration. The consistent reduction
in heparan sulfate in the CSF suggests that the gene therapy may
potentially restore intracellular activity of the I2S enzyme, and
improve neurocognitive development and outcomes for patients," said
Steve Pakola, M.D., Chief Medical
Officer of REGENXBIO. "We are also encouraged by the I2S enzyme
systemic expression observed at the second dose level. We look
forward to presenting additional details from these first two
cohorts at the WORLDSymposium in early 2021."
Dr. Pakola continued, "based on the data from Cohorts 1 and 2,
we plan to initiate enrollment in a third cohort at a higher dose
to further enhance our understanding of the potential treatment
effects of RGX-121, including potential systemic benefit for
patients. We are committed to advancing this novel gene therapy as
quickly as possible to address the significant unmet medical need
for patients with MPS II."
"Patients with MPS II often meet early development milestones,
but delays in many areas of development become apparent at about 18
months of age. I am encouraged by the preliminary evidence of
durable biomarker response in the CNS of patients dosed with
RGX-121, as well as the rates of neurocognitive development seen in
these patients. I'm eager to see additional data from the CNS and
potential systemic effects of this gene therapy," said Paul Harmatz, MD, professor, Department of
Pediatrics, UCSF Benioff Children's Hospital Oakland.
Data Summary and Safety Update
As of November 13, 2020, RGX-121
is reported to be well-tolerated with no drug-related serious
adverse events (SAEs) in eight patients dosed with RGX-121 to date,
including two additional patients who were dosed in the expanded
Cohort 2 that was announced in September
2020.
The interim data announced today includes assessments for the
first six patients in Cohorts 1 and 2. Three patients in Cohort 1
(1.3x1010 genome copies per gram (GC/g) of brain mass)
were dosed at the ages of 5 months (Patient 1), 35 months (Patient
2), and 7 months (Patient 3). Time of post-administration follow-up
ranges from 13 months to two years. Three patients in Cohort 2
(6.5x1010 GC/g of brain mass) were dosed at the ages of
59 months (Patient 4), 40 months (Patient 5), and 25 months
(Patient 6). Time of post-administration follow-up ranges from four
to nine months.
CSF Biomarker Data from Cohorts 1 and 2
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. Consistent, long-term reductions in HS
in the CSF were observed in patients in Cohort 1 up to 2 years
following administration of RGX-121. Patient 1 demonstrated a
45.5% reduction from baseline to 2 years. Patients 2 and 3
demonstrated a reduction of 12.5% and 33.5%, respectively, from
baseline to about one year.
Patients in Cohort 2 similarly demonstrated consistent
reductions in HS in the CSF up to six months after administration
of RGX-121. Patients 4 and 5 demonstrated reductions of HS in the
CSF from baseline at six months of 16.8% and 52.6%, respectively.
Patient 6 demonstrated a 38.0% reduction of HS levels in the CSF
from baseline at four months.
Summary of Neurocognitive Development Data from Cohort
1
Patients in Cohort 1 have continued to acquire developmental
skills up to two years after administration of RGX-121, based on
the neurodevelopment parameters of cognitive, behavioral and
adaptive function as measured by the Bayley1 and
Vineland2 Scales. Neurocognitive and adaptive behavior
scores for Patient 1 at two years and Patient 3 at fourteen months
suggest continued developmental skill acquisition. Patient 2 was
diagnosed with developmental delay prior to dosing with RGX-121,
but cognitive and adaptive behavior assessments at fourteen months
show an increase in age equivalent scores, indicating continued
skill acquisition.
Summary of Systemic Biomarker Data from Cohort 2
Interim data from two patients in Cohort 2 indicates changes in
plasma and urine biomarkers that provide evidence of systemic I2S
enzyme expression. Patient 6 who has never been treated with ERT
had increased levels of I2S enzyme in plasma compared to baseline
beginning two weeks after administration of RGX-121. The increased
levels of I2S enzyme have been sustained out to four months, the
latest timepoint available. Urinary glycosaminoglycans (GAG) levels
were reduced to within normal range in this patient at four months.
Patient 5 continues to receive weekly treatment with ERT, and at
six months, had increased levels of I2S enzyme in plasma compared
to baseline and a reduction of urinary GAG levels to within normal
range.
New data from patients in Cohorts 1 and 2, including additional
neurocognitive development data, will be presented at the
17th Annual WORLDSymposium™, taking
place February 8-12, 2021.
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 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 (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," "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, 2019, 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:
Eleanor Barisser, 212-600-1902
eleanor@argotpartners.com
Media:
David Rosen, 212-600-1902
david.rosen@argotpartners.com
__________________________
|
1 Bayley
Scales of Infant and Toddler B, 3rd Edition (BSID-III)
|
2 Vineland
Adaptive Behavior Scale, 2nd Edition (VABS-II)
|
View original content to download
multimedia:http://www.prnewswire.com/news-releases/regenxbio-announces-positive-interim-data-and-update-for-phase-iii-trial-of-rgx-121-for-the-treatment-of-mps-ii-301189001.html
SOURCE REGENXBIO Inc.