SAN RAFAEL, Calif.,
Sept. 6, 2017 /PRNewswire/
-- BioMarin Pharmaceutical Inc. (NASDAQ:BMRN) announced today
that it presented interim data from the dose escalation arm of a
Phase 1/2 trial for BMN 250, an investigational enzyme replacement
therapy using a novel fusion of recombinant human
alpha-N-acetylglucosaminidase (NAGLU) with a peptide derived from
insulin-like growth factor 2 (IGF2), for the treatment of
Sanfilippo B syndrome or mucopolysaccharidosis IIIB (MPS IIIB) at
the 13th International Congress of Inborn Errors of Metabolism
(ICIEM) 2017. Discovered by BioMarin, BMN 250 is being studied in a
multicenter, international clinical trial evaluating safety and
tolerability, as well as cognitive function of patients with
Sanfilippo B receiving BMN 250. Designed to restore functional
NAGLU activity in the brain, BMN 250 is administered via
intracerebroventricular (ICV) infusion.
In the completed dose escalation portion of the study (Part 1),
which was primarily designed to determine safety and
pharmacodynamic activity of BMN 250, three patients received
escalating doses (30mg, 100mg, 300mg) of BMN 250 over 9 to12
months. Cerebrospinal fluid (CSF) heparan sulfate (HS) levels,
which were markedly elevated at baseline, were reduced to the
non-affected or normal range in all three patients, whether
assessed as total or disease-specific HS. Sanfilippo B patients are
missing one of four enzymes for HS degradation.
In those same patients, abdominal MRI scans showed significantly
enlarged liver size at baseline followed by rapid decreases in
liver size into the normal range for age with BMN 250 treatment,
suggesting that ICV-administered BMN 250 reaches the peripheral
circulation and may have activity in somatic organs. In contrast,
most Sanfilippo B patients enrolled in BioMarin's
concurrently-running observational study (250-901) had increased
liver size at baseline and experienced further increases in liver
size over time.
Two of the three treated patients from the dose escalation arm
showed stabilization or some improvement compared to their pre-dose
baselines in cognitive Development Quotient (DQ), a measure of
cognitive function normalized to age. Patients with untreated
Sanfilippo B usually show progressive decline in DQ.
Interim trial data indicates that ICV-administered BMN 250 was
well-tolerated by Sanfilippo B patients. In the completed dose
escalation portion (Part 1) of the study, the most common
device-related adverse events (AEs) were ICV infection prior to
first BMN 250 infusion, site erythema, CSF pleocytosis and blood
clot in CSF. The most common AEs related to BMN 250 were
pyrexia/fever and bradycardia. There were no serious treatment
emergent AEs. In the ongoing stable dose portion (Part 2) of
the study, there have been no serious device-related AEs reported
to date. Dose-related AEs and serious adverse events (SAEs)
have included vomiting, headache, fever, alteration of
consciousness and CSF pleocytosis; however, all of these events
were self-limited, and all Part 2 patients are currently receiving
300 mg weekly of BMN 250. In both Part 1 and Part 2, the AE profile
is generally consistent with that seen with other ERTs and the ICV
mode of administration.
For a limited time, the slides presented at ICIEM can be
accessed here.
"We are pleased with the preliminary data from the three
patients in the dose escalation stage of the study. Our experience
in ICV administration of an enzyme replacement therapy combined
with more than two decades of experience in developing MPS
treatments has allowed us to reach this important step," said
Hank Fuchs, M.D., President,
Worldwide Research and Development at BioMarin. "We are grateful to
the children and the families who are participating in this early
clinical study."
BMN 250 has been granted orphan drug designation by the European
Commission and the U.S. Food and Drug Administration. BioMarin has
three approved therapies to treat different forms of MPS. BMN 250
is a potential fourth therapy in development for the treatment of
an MPS disorder. BioMarin also has a recently approved enzyme
replacement therapy for CLN2 delivered through intraventricular
administration.
Study Design
The BMN 250 development program consists of three independent
and complementary, multicenter, international studies. BMN 250-901
is an observational study of the progression of Sanfilippo B over
time in children 1-10 years of age with relatively preserved
cognitive function. BMN 250-201 is a Phase 1/2 treatment study
conducted in two parts, with Part 1 focused on safety and
pharmacodynamic activity with dose escalation. Part 2 consists of
eligible patients rolling over from the BMN 250-901 observational
study, in addition to continued treatment of the patients from Part
1 of the study, treated at the highest dose. Efficacy will be
assessed by comparing changes in disease progression in the
observational BMN 250-901 study vs. changes observed in Part 2 of
the BMN 250-201 Phase 1/2 treatment study. A companion study, BMN
250 -902, is a natural history study of the progression of
Sanfilippo B over time in children 0-18 years of age with all
levels of cognitive function.
About BMN 250
BMN 250 is an investigational enzyme replacement therapy using a
novel fusion of recombinant human alpha-N-acetyglucosaminidase
(NAGLU) with a peptide derived from insulin-like growth factor 2
(IGF2) for the treatment of Sanfilippo B syndrome or
mucopolysaccharidosis IIIB (MPS IIIB). Designed to restore
functional NAGLU activity in the brain, BMN 250 is delivered
directly to the fluid surrounding the brain (cerebrospinal fluid)
by an intracerebroventricular infusion.
For additional information regarding the investigational product
BMN 250, please contact BioMarin Medical Information at
medinfo@bmrn.com.
About Sanfilippo B
Sanfilippo B, a lysosomal storage disease, is caused by
deficiency in the enzyme alpha-N-acetyglucosaminidase (NAGLU), one
of the four enzymes required for heparan sulfate (HS) degradation.
There are an estimated 2,000-3,000 patients in existing BioMarin
territories who are living with Sanfilippo B syndrome.
The first symptoms generally appear between the ages of two and
six years old, with behavior disorders, intellectual deterioration,
sleep disorders, and in some cases, very mild dysmorphism. The
neurological involvement becomes more prominent with progressive
loss of motor milestones and communication problems. The prognosis
is poor with death occurring in most cases in the late teens or
early 20s.
About BioMarin
BioMarin is a global biotechnology company that develops and
commercializes innovative therapies for people with serious and
life-threatening rare disorders. The company's portfolio consists
of six commercialized products and multiple clinical and
pre-clinical product candidates.
For additional information, please visit www.BMRN.com.
Information on BioMarin's website is not incorporated by reference
into this press release.
Forward-Looking Statement
This press release contains forward-looking statements about the
business prospects of BioMarin Pharmaceutical Inc., including,
without limitation, statements about the development plans for BMN
250 and expectations regarding the clinical trials for this product
candidate. These forward-looking statements are predictions and
involve risks and uncertainties such that actual results may differ
materially from these statements. These risks and
uncertainties include, among others: results and timing of current
and planned clinical trials of its product candidates; final
analysis of the clinical trial data collected to date, the content
and timing of decisions by the FDA, the EMA and other regulatory
authorities concerning its product candidates; our ability to
manufacture sufficient quantities of BMN 250 for clinical trials,
commercial launch and other preapproval requirements; and those
other risks detailed from time to time under the caption "Risk
Factors" and elsewhere in the Company's Securities and Exchange
Commission (SEC) filings, including the Company's Quarterly Report
on Form 10-Q for the quarter ended June 30,
2017, and future filings and reports by the Company. The
Company undertakes no duty or obligation to update any
forward-looking statements contained in this press release as a
result of new information, future events or changes in its
expectations.
BioMarin® is a registered trademarks of BioMarin Pharmaceutical
Inc.
Contact:
|
|
Investors:
|
Media:
|
Traci
McCarty
|
Debra
Charlesworth
|
BioMarin
Pharmaceutical Inc.
|
BioMarin
Pharmaceutical Inc.
|
(415)
455-7558
|
(415)
455-7451
|
View original content with
multimedia:http://www.prnewswire.com/news-releases/biomarin-presents-interim-data-of-phase-12-study-of-bmn-250-for-treatment-of-sanfilippo-b-syndrome-mps-iiib-at-13th-international-congress-of-inborn-errors-of-metabolism-iciem-2017-300514453.html
SOURCE BioMarin Pharmaceutical Inc.