- RGX-121, a potential one-time gene therapy for the treatment
of MPS II, continues to be well-tolerated with no drug-related SAEs
across three dose levels
- Additional data from patients in Cohort 3 using pivotal
program dose level continue to demonstrate largest reductions in
CSF GAGs, continuing to approach normal levels at 48 weeks
- New, longer-term clinical measures demonstrated continued
improvement in neurodevelopmental and daily activity skill
acquisition up to three years after RGX-121 administration
- Positive interim data continues to support plan to file
Biologics License Application in 2024 using the accelerated
approval pathway
ROCKVILLE, Md., Feb. 22,
2023 /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 19th Annual WORLDSymposium™.
"These new results demonstrate sustained reductions in CSF GAGs
and an encouraging, long-term clinical profile of RGX-121 up to
three years," said Steve Pakola,
M.D., Chief Medical Officer of REGENXBIO. "GAGs measured in CSF,
specifically heparan sulfate, reflect disease manifestations in the
CNS and are a direct cause of disease pathophysiology. Our data
provide additional evidence to support the finding that meaningful
changes in CSF heparan sulfate is an appropriate and reliable
surrogate endpoint reasonably likely to predict the clinical
benefit of CNS-targeted therapies for MPS II. We are excited to
have taken RGX-121 into a pivotal program and plan to file a
Biologics License Application in 2024 using the accelerated
approval pathway."
"Treatment options to address the neurological manifestations of
MPS II remain a significant unmet medical need for patients," said
Can Ficicioglu, M.D., Ph.D., Professor of Pediatrics at the
Perelman School of Medicine, University of
Pennsylvania. "The data presented today are encouraging and
continue to show the potential of a one- time gene therapy to
provide meaningful, durable clinical benefits to the MPS II
community. I look forward to continuing to follow RGX-121 as it
progresses through the pivotal program."
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 were from the Phase
I/II portion of the CAMPSIITE trial in which 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 January
3, 2023, 15 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=5).
Data Summary and Safety Update
As of January 3, 2023, RGX-121 was
reported to be well tolerated across all cohorts with no
drug-related serious adverse events (SAEs) in 15 patients dosed.
Time of post-administration follow-up ranges from eight weeks to
more than three years. Thirteen 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; five of these
patients remain discontinued from ERT at last time point available,
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. CSF GAGs have the potential to be considered a surrogate
endpoint 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 cohorts demonstrated reductions
of CSF HS from baseline 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, 48.9% in Cohort 2 and 64.7% in
Cohort 3.
Similarly, dose-dependent reductions of CSF HS D2S6 from
baseline were observed at last time point available in the majority
of patients, with Cohort 3 patients approaching normal levels at 48
weeks. All three cohorts demonstrated a reduction in HS D2S6 with
dose-dependent reductions seen at Weeks 8, 24, and 48. Median
reductions from baseline of 31.9% in Cohort 1, 71.9% in Cohort 2
and 83.3% in Cohort 3 were seen at Week 48.
In addition, I2S protein concentration in the CSF, which was
undetectable in all patients prior to dosing, was measurable in 10
of 11 Cohort 2 and 3 patients after RGX-121 administration.
Neurodevelopmental and Systemic
Data
Improvements in neurodevelopmental function and
caregiver reported outcomes demonstrated CNS activity on two
developmental scales up to three years after RGX-121
administration. As measured by the Bayley Scales of Infant and
Toddler Development, 3rd Edition (BSID-III), the majority of
participants with baseline function ≥-2 standard deviations (SD)
from the normative mean had developmental function that remained
within that range on at least two domains. The majority of
participants with baseline function below -2SD from the normative
mean stabilized or had an increase of ≥ 3 months in age equivalent
scores on cognitive, expressive language or fine motor subtests. As
measured by the Vineland Adaptive Behavior Scales Second Edition
(VABS-II), the majority of participants demonstrated stabilization
or ongoing skill acquisition on age-appropriate subtests of
communication, daily living and socialization.
Additionally, evidence of systemic enzyme expression and
biomarker activity was observed in all 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 2023 WORLDSymposium
will be available under the Presentations & Publications page
in the Media section of REGENXBIO's website located at
www.regenxbio.com. Dr. Ficicioglu will share this data in a
platform presentation at the WORLDSymposium Sunday, February 26, 2023, at 9 a.m. ET.
About the CAMPSIITE™ Trial
CAMPSIITE is a Phase
I/II/III multicenter, open-label trial enrolling boys with MPS II,
aged four months up to five years of age. As part of a pivotal
program expansion, 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) D2S6, 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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