- New data in Cohort 3
using pivotal program dose level demonstrates largest median
reduction in CSF GAGs, continuing to approach normal levels at 48
weeks
- RGX-121, a
one-time gene therapy for MPS II, continues to be well-tolerated
with no drug-related SAEs across three dose
levels
- Positive
interim data supports recently announced plan to file Biologics
License Application in 2024 using the accelerated approval
pathway
ROCKVILLE, Md., Aug. 31,
2022 /PRNewswire/ -- REGENXBIO Inc. (Nasdaq: RGNX)
today announced additional positive interim data from the Phase
I/II/III CAMPSIITE™ 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 results were presented at
the Society for the Study of Inborn Errors of Metabolism (SSIEM)
Annual Symposium.
"We are pleased to share new, positive interim data from our
Phase I/II/III CAMPSIITE trial that continues to demonstrate
encouraging reductions of CSF GAGs and supports the selection of
dose level 3 for our pivotal program," said Steve Pakola, M.D., Chief Medical Officer of
REGENXBIO. "This interim data of Cohorts 1-3 demonstrate
dose-dependent reductions in CSF GAGs, key biomarkers of I2S enzyme
activity, in additional patients and at longer timepoints than
previously presented. RGX-121 has also demonstrated positive impact
on neurodevelopmental function. We believe the data supports our
plan to advance RGX-121 as quickly as possible using the
accelerated approval pathway with the aim of providing a
much-needed new treatment option for the MPS II community."
"RGX-121 continues to demonstrate compelling data showing its
potential to impact the neurodevelopmental decline of MPS II
patients, which remains an unmet need for most affected
individuals," said Roberto Giugliani, M.D., Ph.D., Professor,
Department of Genetics, UFRGS, Medical Genetics Service, HCPA,
Porto Alegre, Brazil. "A
successful gene therapy with the potential to provide advantages
over current standard of care is something that could provide a
meaningful treatment option to the MPS II patient community. I look
forward to continuing to follow this trial as the recently
announced pivotal program progresses."
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. Data presented at SSIEM was from the
Phase I/II portion of the CAMPSIITE trial where the primary
endpoint is to evaluate the safety of RGX-121. Secondary and
exploratory endpoints include cerebral spinal fluid (CSF)
glycosaminoglycans (GAGs), neurodevelopmental assessments,
caregiver reported outcomes and systemic biomarkers. RGX-121 is
administered directly to the central nervous system (CNS). As of
August 1, 2022, patients had been
treated across three dose levels, 1.3x1010 genome copies
per gram (GC/g) of brain mass (n=3), 6.5x1010 GC/g of
brain mass (n=7), and 2.9x1011 GC/g of brain mass
(n=4).
Data Summary and Safety
Update
As of August 1, 2022, RGX-121 is
reported to be well-tolerated across all cohorts with no
drug-related serious adverse events (SAEs) in 14 patients dosed
with RGX-121. Time of post-administration follow-up ranges from
eight weeks to two years. Eleven patients have completed the
48-week immunosuppression regimen per study protocol. Twelve
patients were receiving weekly, intravenous enzyme replacement
therapy (ERT) at the time of enrollment, per standard of care;
three of these patients have discontinued ERT, per investigator
discretion, as allowed in the protocol.
CSF GAGs Data
Biomarker data from patients in all three cohorts indicate
encouraging, dose-dependent reductions of CSF GAGs following
one-time administration of RGX-121. Heparan sulfate (HS) and D2S6,
a component of HS closely correlated with severe MPS II, are GAGs
that are key biomarkers of I2S enzyme activity and are being
measured in the CSF at baseline and after administration of
RGX-121. GAGs in the CSF have the potential to be considered a
surrogate biomarker that is reasonably likely to predict clinical
benefit in MPS II disease under the accelerated approval pathway,
as buildup of GAGs in the CSF of MPS II patients correlates with
clinical manifestations, including neurodevelopmental deficits.
The majority of patients in all three cohorts demonstrated
reductions of HS in the CSF following RGX-121 administration at the
last time point available with dose-dependent reductions seen at
Weeks 8, 24, and 48 post RGX-121 administration. At Week 48, median
reduction of CSF HS from baseline was 33.5% in Cohort 1, 52.9% in
Cohort 2 and 62.5% in Cohort 3.
Similarly, dose-dependent reductions of CSF HS D2S6 were
observed at last time point available following RGX-121
administration in the majority of patients, with Cohort 3 patients
approaching normal levels at 48 weeks. All three cohorts
demonstrated reduction in HS D2S6 with dose-dependent reductions
seen at Weeks 8, 24, and 48. Median reduction from baseline of
31.9% in Cohort 1, 69.4% in Cohort 2 and 83.1% in Cohort 3 was seen
at Week 48.
In addition, I2S protein concentration in the CSF, which was
undetectable in all patients prior to dosing, was measurable in
Cohort 2 and 3 patients after RGX-121 administration.
Neurodevelopmental and Systemic
Data
As previously reported at the 2022 WORLDSymposium™,
improvements in neurodevelopmental function and caregiver reported
outcomes in Cohorts 1 and 2 demonstrated CNS activity up to 2 years
after RGX-121 administration. Additionally, evidence of systemic
enzyme expression and biomarker activity was observed in patients
across all three cohorts following RGX-121 administration. The
majority of patients demonstrated increases in I2S protein
concentration levels in plasma following administration of RGX-121.
Total urine GAG measures demonstrated evidence of a systemic effect
of RGX-121, independent of ERT treatment.
The study findings presented at the SSIEM Annual Symposium will
be available under the Presentations & Publications page in the
Media section of REGENXBIO's website located at
www.regenxbio.com.
About the CAMPSIITE™ Trial
CAMPSIITE is a multicenter, open-label trial enrolling boys with
MPS II, aged 4 months up to five years of age. CAMPSIITE is
expected to enroll up to 10 MPS II patients to support the BLA
filing using the accelerated approval pathway, with the potential
to enroll additional patients. These patients will receive a dose
of 2.9x1011 GC/g of brain mass of RGX-121, which is the
same dose being evaluated in Cohort 3 of the Phase I/II trial. The
pivotal program is using commercial-scale cGMP material from
REGENXBIO's proprietary, high-yielding suspension-based
manufacturing process, named NAVXPress™. In addition to measuring
GAGs in the CSF, the trial will continue to collect
neurodevelopmental data and caregiver-reported outcomes.
CAMPSIITE is a global trial, which is expected to include sites
in the United States, Brazil and Canada. REGENXBIO has begun dosing patients in
the pivotal program.
About RGX-121
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 (GAGs), including heparan sulfate (HS) in
tissues which ultimately results in cell, tissue, and organ
dysfunction, including in the central nervous system (CNS). MPS II
is estimated to occur in 1 in 100,000 to 170,000 births. 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 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,
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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