CALABASAS, Calif., Feb. 8, 2018 /PRNewswire/ -- ArmaGen, Inc.,
a privately held biotechnology company focused on developing
groundbreaking therapies to treat severe neurological disorders,
today reported full 52-week results from a Phase 2 proof-of-concept
study with AGT-181, the company's investigational therapy for the
treatment of mucopolysaccharidosis type I, or MPS I (also known as
Hurler, Hurler-Scheie and Scheie syndromes). Data presented
today at the 14th Annual WORLDSymposium in
San Diego, California, suggest
that AGT-181 stabilized the neurocognitive development quotient
(DQ) in patients with severe MPS I. The data validate previous
findings that demonstrated the ability of ArmaGen's proprietary
drug delivery technology to transport biopharmaceuticals across the
blood-brain barrier (BBB) and provide therapeutic benefit to
patients with severe MPS I.
In an oral presentation entitled, "Safety and clinical efficacy
of AGT-181, a brain penetrating human insulin receptor
antibody-iduronidase fusion protein, in a 52-week study with
pediatric patients with mucopolysaccharidosis type I," Roberto
Giugliani, M.D., Ph.D., of Hospital de Clínicas in Porto Alegre, Brazil, reported the
following:
- Stabilization of several measures of neurocognitive function as
measured by DQ -- a numerical indicator of a child's growth to
maturity across a range of cognitive competencies -- in children
treated with AGT-181 for one year
- On a somatic level, AGT-181 stabilized urinary
glycosaminoglycans, reduced liver and spleen volume including in
patients previously exposed to laronidase, and further improved
shoulder range of motion
- AGT-181 displayed a favorable long-term safety and tolerability
profile. Most frequent drug-related adverse events were infusion
reactions (1.7%) and transient hypoglycemia (2.8% at 1 mg/kg and 3
mg/kg).
"The full results from this Phase 2 study validate our
preliminary findings that AGT-181 crosses the blood-brain barrier
and benefits neurocognitive function in children with severe MPS
I," said Dr. Giugliani. "Whereas the existing enzyme replacement
therapy improves many of the somatic manifestations of MPS I, its
inability to cross the blood-brain barrier prevents it from
addressing the severe and progressive neurological symptoms of the
most severe form of the disorder. Now that we have demonstrated
proof of concept, a controlled phase 3 clinical trial is warranted
to examine long term impact in cognition in MPS I patients with CNS
involvement."
At the 13th Annual WORLDSymposium in 2017, Dr.
Giugliani presented preliminary evidence of cognitive improvement
in age-equivalent function in the first five children with MPS I
who were enrolled in the Phase 2 study, after six months of
treatment with AGT-181. This year's presentation included the full
set of 52-week data from all 11 children (age 2 years or older)
enrolled in the trial. Nine of eleven patients had previously been
treated with enzyme replacement therapy and one had received a stem
cell transplant which had failed engraftment. The children received
weekly intravenous infusions of AGT-181 at doses of 1.0, 3.0 or 6.0
mg/kg. The investigators conducted developmental age-appropriate
neurocognitive testing at 13, 26 and 52 weeks of treatment,
utilizing the following validated neurocognitive assessments tests:
the Bayley Scales of Infant Development Third Edition (BSID-III) or
the Kaufman Assessment Battery for Children (KABC-II), and the
Vineland Adaptive Behavior Scales Second Edition (VABS-II).
Together, these tests represent a summation of scores reflecting
cognitive, language and motor skills.
Dr. Giugliani reported stabilization of the cognitive DQ with no
net decline after 52 weeks of AGT-181, as would normally be
expected for the severe MPS I patients that have not undergone
successful hematopoietic stem cell transplantation. He also
presented stabilization of cortical grey matter volume at 52 weeks
of AGT-181 therapy. Among the nine patients previously on
laronidase ERT for 1-12 years, AGT-181 was associated with further
improvements in somatic disease control, based on further
reductions in liver and spleen volume, and increases in shoulder
flexion and extension range of motion. Additionally, the anti-drug
antibody (ADA) profile with AGT-181 treatment was comparable to
that observed with laronidase, Dr. Giugliani reported.
AGT-181 was well tolerated. Out of more than 570 infusions,
there were 10 infusion-related reactions (IRRs) – an incidence rate
of 1.7%. Sixty percent of IRRs were observed in a single patient
not previously on ERT; this patient developed tolerance to AGT-181
by the tenth week of therapy. Other drug-related adverse events
(AEs) included transient hypoglycemia (5.9% incidence) that
resolved within 10-20 minutes following a snack or glucose
administration. Most hypoglycemic events (62%) occurred in patients
taking high-dose (6 mg/kg) AGT-181 therapy. Among patients
receiving an infusion dose of 1-3 mg/kg, the incidence of
hypoglycemia was 2.8%. The investigators observed no serious AEs
that were likely to be drug-related.
"By confirming our initial findings of neurocognitive
stabilization/improvement in children with MPS I, the full results
from the Phase 2 proof-of-concept trial – coupled with our recent
receipt of a Fast Track designation from the FDA – sustain the
momentum of finding a new treatment option for patients with MPS
I," said Mathias Schmidt, Ph.D.,
Chief Executive Officer of ArmaGen. "The latest results add to the
growing body of evidence that our proprietary 'Trojan Horse'
technology can deliver the missing enzyme into the CNS of patients
and benefit neurocognitive function. We are most grateful to the
patients and families who participated in the Phase 2 study."
About Mucopolysaccharidosis I (MPS I)
MPS I is a rare,
hereditary, lysosomal storage disease that arises from a deficiency
or absence of the enzyme iduronidase (IDUA), which is needed to
break down complex sugars produced by the body. MPS I affects
approximately 3,000-4,000 patients worldwide. The most severe form
of MPS I, Hurler syndrome affects several organs, including the
brain, resulting in somatic and neurological manifestations that
can include developmental delay, progressive mental decline, loss
of physical function, impaired language development, airway
obstruction, corneal and retinal damage, carpal tunnel syndrome,
and restricted joint movement. Attenuated or less severe forms of
MPS I include Hurler-Scheie and Scheie syndromes. Patients with
Hurler-Scheie syndrome may suffer from mild cognitive impairment or
problems with attention. Patients with Scheie syndrome generally
have a later onset, milder symptoms, and a slower disease
progression, usually without CNS involvement, although they can
develop significant morbidity.
About AGT-181
AGT‑181 is a novel, investigational
enzyme replacement therapy for the treatment of both somatic and
cognitive symptoms in patients with MPS I. ArmaGen developed
AGT-181 by re-engineering the enzyme iduronidase (IDUA) as fusion
protein with an immunoglobulin G (IgG) antibody targeting the
insulin receptor. Utilizing ArmaGen's proprietary "Trojan Horse"
technology, AGT-181 takes advantage of the body's natural system
for transporting proteins and other large molecules non-invasively
across the blood-brain barrier (BBB), in this case by binding the
same receptor that transports insulin across the BBB into the
brain.
In November 2017, the U.S. Food
and Drug Administration (FDA) granted Fast Track designation to
AGT-181. A Fast Track designation is aimed at accelerating the
development and regulatory review of drugs meeting urgent needs. To
receive the designation, a therapy candidate must demonstrate an
advantage over currently available treatments such as superior
efficacy, ability to meet an unmet medical need, or fewer side
effects.
About ArmaGen
ArmaGen, Inc., is a privately held
biotechnology company focused on developing groundbreaking
therapies for severe neurological disorders. The company is
developing a robust pipeline of innovative therapies for the
treatment of lysosomal storage disorders including neurological
symptoms such as Hurler syndrome (MPS I), Hunter syndrome (MPS II),
metachromatic leukodystrophy, Sanfilippo A and B syndromes, as well
as other diseases with severe CNS manifestations. ArmaGen's
pipeline is based on decades of scientific leadership in
engineering therapies to cross the blood-brain barrier and a
dominant intellectual property portfolio. The company is advancing
its pipeline through licensing and collaboration agreements,
in-house development programs, and other partnering opportunities.
For more information, visit www.armagen.com.
Contacts:
ArmaGen, Inc.
Derek
Kelaita
Vice President, Business Development
818-252-8200
dkelaita@armagen.com
For media inquiries:
Alex Van Rees
SmithSolve LLC
973-442-1555 ext. 111
alex.vanrees@smithsolve.com
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SOURCE ArmaGen, Inc.