Results From Investigator-Sponsored Trials Presented at SSIEM Conference
Kuvan Patients Show Improvements in Neurocognitive Functioning, Mood and Behavior
NOVATO, Calif., Sept. 1 /PRNewswire-FirstCall/ -- BioMarin
Pharmaceutical Inc. (NASDAQ:BMRN) announced today that results from
investigator-sponsored studies on Kuvan (sapropterin
dihydrochloride) are being presented at the 2010 Annual Symposium
of the Society for The Study of Inborn Errors of Metabolism
(SSIEM), August 31st-September 3rd in Istanbul, Turkey.
Investigators reported that PKU patients taking Kuvan showed
improvements in brain functioning, mood and behaviors.
"While these investigator-sponsored studies were conducted in a
small number of subjects, the results indicate benefits beyond
lowering blood Phe levels, and we hope to document similar
neurocognitive improvements in subjects with PKU in our recently
initiated Phase 3b Kuvan outcomes study," said Dr. Hank Fuchs,
Chief Medical Officer of BioMarin. "If successful, the data will be
submitted in support of a label amendment."
Highlights of Investigator-Sponsored Studies:
Neurocognitive findings in individuals with Phenylketonuria and
treatment with sapropterin dihydrochloride (BH4) (White, et al;
Washington University, St. Louis): Baseline findings indicate that
executive performance is worse for subjects with PKU as compared to
non-PKU subjects across a range of executive functions such as
inhibitory control, strategic processing and working memory. The
results of this exploratory study suggest improvements in executive
abilities following treatment with sapropterin.
Brain function in individuals with PKU treated with Kuvan:
Evidence from functional magnetic resonance imaging (Christ, et al;
University of Missouri-Columbia, USA): At baseline, irregularities
in neural activation were observed in subjects with PKU in the
prefrontal cortex (PFC) and other brain regions as compared to
subjects without PKU. At four weeks, two early-treated PKU
participants responded to Kuvan with a >20% reduction in
phenylalanine levels and also showed improved activation for a
region in the orbitomedial PFC.
Pilot study to evaluate the effects of Kuvan on adult
individuals with Phenylketonuria with measurable maladaptive
behaviors (Moseley, et al; University of Southern California/Keck
School of Medicine): Preliminary six-month data in ten subjects
with measurable maladaptive behaviors showed that while there was a
small decrease in blood Phe concentrations there was a large
decrease in the Phe/Tyr ratio. Additionally, improvements were
measured in all negative behaviors, most specifically, irritability
and rage.
About Kuvan
Kuvan® (sapropterin dihydrochloride) Tablets are indicated
in the United States to reduce blood phenylalanine (Phe) levels in
patients with hyperphenylalaninemia (HPA) due to
tetrahydrobiopterin- (BH4-) responsive phenylketonuria (PKU). Kuvan
is to be used in conjunction with a Phe-restricted diet. The active
ingredient in Kuvan, sapropterin dihydrochloride, is the synthetic
form of 6R-BH4 (tetrahydrobiopterin), a naturally occurring enzyme
cofactor that works in conjunction with phenylalanine hydroxylase
(PAH) to metabolize Phe. Kuvan has received orphan drug designation
from both the U.S. Food and Drug Administration (FDA) and the
European Medicines Agency (EMEA). Kuvan has received seven years of
orphan exclusivity in the United States and ten years of market
exclusivity in the E.U.
Important Safety Information
Prolonged exposure to elevated blood Phe levels in PKU patients
can result in severe neurologic damage. The initiation of KUVAN
therapy does not eliminate the need for careful monitoring of blood
Phe levels and ongoing dietary management.
Some patients receiving Kuvan can experience significant drops
in blood Phe levels. Patients should be monitored closely to ensure
that blood Phe levels do not fall too low.
Not all patients with PKU respond to treatment with Kuvan.
Response to treatment can only be determined by a therapeutic trial
of Kuvan.
Kuvan has not been studied in patients with liver or renal
impairment. Patients who have these conditions should be carefully
monitored when receiving Kuvan. Caution should be used with the
administration of Kuvan to patients who are receiving levodopa and
drugs that affect nitric oxide-mediated vasorelaxation or folate
metabolism.
The most serious adverse reactions reported during Kuvan
administration (regardless of relationship to treatment) were
gastritis, spinal cord injury, streptococcal infection, testicular
carcinoma, and urinary tract infection. Mild to moderate
neutropenia was also noted. The most common adverse reactions were
headache, diarrhea, abdominal pain, upper respiratory tract
infection, pharyngolaryngeal pain, vomiting, and nausea.
About PKU
PKU, a genetic disorder affecting approximately 50,000 diagnosed
patients in the developed world, is caused by a deficiency of the
enzyme phenylalanine hydroxylase (PAH). PAH is required for the
metabolism of phenylalanine, an essential amino acid found in most
protein-containing foods. If the active enzyme is not present in
sufficient quantities, Phe accumulates to abnormally high levels in
the blood and becomes toxic to the brain, resulting in a variety of
complications including severe mental retardation and brain damage,
mental illness, seizures, tremors, and limited cognitive ability.
As a result of newborn screening efforts implemented in the 1960s
and early 1970s, virtually all PKU patients under the age of 40 in
developed countries have been diagnosed at birth. To learn more
about PKU, please visit www.PKU.com. Information on this website is
not incorporated by reference into this press release.
About BioMarin
BioMarin develops and commercializes innovative
biopharmaceuticals for serious diseases and medical conditions. The
company's product portfolio comprises four approved products and
multiple clinical and pre-clinical product candidates. Approved
products include Naglazyme® (galsulfase) for
mucopolysaccharidosis VI (MPS VI), a product wholly developed and
commercialized by BioMarin; Aldurazyme® (laronidase) for
mucopolysaccharidosis I (MPS I), a product which BioMarin developed
through a 50/50 joint venture with Genzyme Corporation; Kuvan®
(sapropterin dihydrochloride) Tablets, for phenylketonuria (PKU),
developed in partnership with Merck Serono, a division of Merck
KGaA of Darmstadt, Germany; and Firdapse(TM) (amifampridine
phosphate), which has been approved by the European Commission for
the treatment of Lambert Eaton Myasthenic Syndrome (LEMS). Other
product candidates include GALNS (N-acetylgalactosamine
6-sulfatase), which is currently in Phase I/II clinical development
for the treatment of MPS IVA and PEG-PAL (PEGylated recombinant
phenylalanine ammonia lyase), which is currently in Phase II
clinical development for the treatment of PKU. For additional
information, please visit www.BMRN.com. Information on BioMarin's
website is not incorporated by reference into this press
release.
BioMarin®, Naglazyme® and Kuvan® are registered
trademarks of BioMarin Pharmaceutical Inc.
Firdapse(TM) is a trademark of BioMarin Huxley Ltd. Aldurazyme® is a registered trademark of BioMarin/Genzyme LLC. Contact: Eugenia Shen BioMarin Pharmaceutical Inc. (415) 506-6570
Source: BioMarin Pharmaceutical Inc.
CONTACT: Eugenia Shen of BioMarin Pharmaceutical Inc.,
+1-415-506-6570
Web Site: http://www.bmrn.com/
Posted: September 2010
