Alexion Presents New SBC-103 (rhNAGLU enzyme) Phase 1/2 Data on Brain MRI and Neurocognitive Assessments in Patients with Mucopolysaccharidosis IIIB (MPS IIIB)

NEW HAVEN, Conn.–(BUSINESS WIRE)–Alexion Pharmaceuticals, Inc. (Nasdaq:ALXN) announced today that
researchers presented new data from an ongoing open-label, Phase 1/2
trial of intravenous (IV) SBC-103 (rhNAGLU enzyme), an investigational
enzyme replacement therapy, in children with mucopolysaccharidosis IIIB
(MPS IIIB, also known as Sanfilippo syndrome type B), a genetic,
progressive, and devastating rare lysosomal storage disease. Preliminary
evidence, based on brain scans (MRI) and neurocognitive assessments at
24 weeks, showed the potential for disease stabilization in patients
with MPS IIIB treated with SBC-103.¹ These data were
presented at the 14^th International Symposium on MPS and
Related Diseases in Bonn, Germany.
MPS IIIB is caused by genetic mutations that result in a marked decrease
in N-acetyl-α-D-glucosaminidase (NAGLU) enzyme activity, leading to
abnormal accumulation of heparan sulfate (HS) in the brain and other
organs, as well as progressive brain atrophy with cortical gray matter
(CGM) volume loss.^2-5 This results in severe neurocognitive
decline, behavioral disturbances, speech loss, increasing loss of
mobility, and premature death.⁶ At present there is no
treatment for this disorder. MPS IIIB typically presents in children
during the first few years of life, and these children have a greater
than 50 percent mortality rate by 17 years of age.⁷
“MPS IIIB is a devastating and life-threatening disorder, with no
available treatments, and has a severe and progressive impact on the
cognitive function of children suffering with the disease,” said Martin
Mackay, Ph.D., Executive Vice President and Global Head of R&D at
Alexion. “These new data presented today suggest the potential of
SBC-103 to cross the blood-brain barrier when administered intravenously
and provide preliminary evidence of potential dose-dependent disease
stabilization at 24 weeks in children with MPS IIIB.”
Researchers presented preliminary results for volumetric brain MRI and
neurocognitive assessments performed after 24 weeks of IV SBC-103 at
0.3, 1, or 3 mg/kg every other week (QOW). MRI scans for those dosed at
3 mg/kg showed that 3 out of 4 patients had an increase or no change
(-1% to +1%) in CGM volume compared to baseline suggesting a potential
for disease stabilization at this dose. In the 1 mg/kg group and 0.3
mg/kg group, MRI scans showed that 2 out of 3 and 0 out of 3 patients
respectively had an increase or no change in CGM volume compared to
baseline. In the neurocognitive assessments for the 3 mg/kg group, 3 out
of 4 patients had an increase in both mental age equivalent (AEq) and
developmental quotient (DQ) compared to baseline. For the 1 mg/kg group,
2 out of 4 patients had an increase in both AEq and DQ compared to
baseline, and for 0.3 mg/kg group, 1 out of 3 patients had an increase
in both AEq and DQ compared to baseline. Overall, response profiles
among the 3 mg/kg treatment groups suggest a potential dose effect as
compared to the 0.3 mg/kg and 1 mg/kg groups.¹
“These new preliminary data from the brain MRI and neurocognitive
assessments of children with MPS IIIB show, for the first time, the
potential for disease stabilization following intravenous administration
of SBC-103,” said Chester B. Whitley, Ph.D., M.D., Department of
Pediatrics, University of Minnesota, Minneapolis, U.S. “In addition to
the evidence of heparan sulfate reduction in cerebrospinal fluid, these
findings support the continued advancement of this clinical program, and
dose escalation to 5 mg/kg and 10 mg/kg for all patients in the study
with this severe and progressive rare disease.”
Eleven children with MPS IIIB (ages 2 years to 10 years at study entry)
were enrolled in this first-in-human study, which included three
parallel dosing groups of intravenous SBC-103 (0.3, 1.0 and 3.0 mg/kg
QOW). The primary endpoint of the ongoing trial is safety and
tolerability, and key secondary endpoints presented at MPS 2016
include effect of SBC-103 on total HS levels in cerebrospinal fluid
(CSF) and serum, brain structures (MRI) and neurocognitive status, and
pharmacokinetic (PK) profile of SBC-103.
During 24 weeks of treatment with SBC-103 at the highest dose of 3
mg/kg, most adverse events (AEs) were mild in severity and no patient
discontinued the study. Two patients experienced a total of four serious
AEs (bacteremia, pyrexia, staphylococcal bacteremia, and cyanosis
[pre-treatment]) that were deemed not related to SBC-103. Seven
infusion-associated reactions occurred in three patients (pyrexia,
chills, hypertension, and tachycardia).¹
As previously presented at the 12^th Annual WORLDSymposium^TM,
patients treated with SBC-103 had a 26.2 percent mean reduction from
baseline in total HS levels in CSF at 24 weeks in the highest dose
studied (3 mg/kg QOW). Additionally, at week 24, patients in the 0.3
mg/kg and 1.0 mg/kg groups had a 10.9 percent mean increase and a 0.4
percent mean decrease in HS CSF, respectively. HS reduction in CSF was
linearly correlated with SBC-103 serum PK exposures. Total change from
baseline in serum HS was -39.6 percent, -53.9 percent and -40.5 percent
for 0.3 mg/kg, 1 mg/kg, and 3 mg/kg groups, respectively.⁸
About Mucopolysaccharidosis IIIB (MPS IIIB)
MPS IIIB (also known as Sanfilippo syndrome type B) is a genetic,
progressive, and devastating rare lysosomal storage disease. In patients
with MPS IIIB, genetic mutations result in a marked decrease in
N-acetyl-α-D-glucosaminidase (NAGLU) enzyme activity, which leads to the
accumulation of heparan sulfate (HS) in the brain and other organs, as
well as progressive brain atrophy with cortical gray matter (CGM) volume
loss.^2-5 The accumulation of abnormal HS results in
neurocognitive decline, behavioral disturbances, speech loss, increasing
loss of mobility, and premature death.⁶ MPS IIIB typically
presents in children during the first few years of life, and patients
have a greater than 50 percent mortality rate by 17 years of age.⁷
There are no approved treatments for patients with MPS IIIB. Current
supportive care is palliative for behavioral problems, sleep
disturbances, seizures, and other complications, and does not address
the root cause of MPS IIIB or stop disease progression.^6,7
About SBC-103
SBC-103 (rhNAGLU enzyme) is an enzyme replacement therapy (ERT) being
investigated in a Phase 1/2 trial for patients with MPS IIIB. It is a
recombinant form of the N-acetyl-α-D-glucosaminidase (NAGLU) enzyme
intended to reduce accumulated heparan sulfate by replacing the missing
or deficient NAGLU enzyme. SBC-103 was granted orphan designation by the
U.S. Food and Drug Administration (FDA) in April 2013 and by the
European Commission in June 2013. It received Fast Track designation by
the FDA in January 2015.
SBC-103 utilizes Alexion’s proprietary protein expression platform, a
novel production process that has the potential to enable ERTs to cross
the blood-brain barrier. Alexion is evaluating the use of this platform
in the development of ERTs for severe and devastating lysosomal storage
diseases, including those that have central nervous system
manifestations.
About Alexion
Alexion is a global biopharmaceutical company focused on developing and
delivering life-transforming therapies for patients with devastating and
rare disorders. Alexion is the global leader in complement inhibition
and has developed and commercializes the first and only approved
complement inhibitor to treat patients with paroxysmal nocturnal
hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), two
life-threatening ultra-rare disorders. In addition, Alexion’s metabolic
franchise includes two highly innovative enzyme replacement therapies
for patients with life-threatening and ultra-rare disorders,
hypophosphatasia (HPP) and lysosomal acid lipase deficiency (LAL-D).
Alexion is advancing the most robust rare disease pipeline in the
biotech industry with highly innovative product candidates in multiple
therapeutic areas. This press release and further information about
Alexion can be found at: www.alexion.com
[ALXN-G]
Forward-Looking Statements
This news release contains forward-looking statements, including
statements related to potential medical benefits of SBC-103 for
mucopolysaccharidosis IIIB (MPS IIIB). Forward-looking statements are
subject to factors that may cause Alexion’s results and plans to differ
from those expected, including for example, risks and uncertainties of
drug development, decisions of regulatory authorities regarding
marketing approval or material limitations on the marketing of SBC-103
for MPS IIIB, delays in arranging satisfactory manufacturing
capabilities and establishing commercial infrastructure for SBC-103 for
MPS IIIB, the possibility that results of clinical trials are not
predictive of safety and efficacy results of SBC-103 in broader or
different patient populations, the risk that estimates regarding the
number of patients with MPS IIIB are inaccurate, the possibility that
clinical trials of our product candidates could be delayed or that
additional research and testing is required by regulatory agencies, and
a variety of other risks set forth from time to time in Alexion’s
filings with the Securities and Exchange Commission, including but not
limited to the risks discussed in Alexion’s Quarterly Report on Form
10-Q for the period ended March 31, 2016 and in our other filings
with the U.S. Securities and Exchange Commission. Alexion does not
intend to update any of these forward-looking statements to reflect
events or circumstances after the date hereof, except when a duty arises
under law.