BioMarin Pharmaceutical
Inc. (Nasdaq and SWX: BMRN) today announced that the first patient has
initiated treatment in the Phase 2a clinical study of 6R-BH4 (sapropterin
dihydrochloride) for the treatment of sickle cell disease (SCD). The
company expects to announce data from this study in the first half of 2008.

“The sickle cell disease indication fits well strategically with our
focus on rare, undertreated genetic diseases. SCD is an orphan disease with
70,000 to 100,000 patients in the United States, according to the CDC. It
is well- diagnosed at birth, but there is only one approved drug treatment
option currently available which is used by a minority of patients due to
toxicity problems,” said Jean-Jacques Bienaime, Chief Executive Officer of
BioMarin. “6R-BH4 is an essential enzyme cofactor that is involved in the
production of nitric oxide, a molecule that has been shown to play a role
in the regulation of endothelial function. Studies of SCD patients suggest
that endothelial dysfunction may play a role in sickle cell disease, and
studies in an animal model of SCD suggest the potential utility of 6R-BH4
in the treatment of the vascular problems found in this disease.”

The Phase 2a multi-center, open-label study is designed to assess the
safety and biologic activity of escalating doses of 6R-BH4 in patients with
SCD. The study will be conducted at approximately six U.S. sites and will
enroll approximately 40 subjects. Among other eligibility criteria, to
participate in the study, SCD patients must be at least 15 years of age and
not receiving hydroxyurea therapy. Study patients will initially receive a
low, once daily oral administration of 6R-BH4 (2.5 mg/kg) and will
gradually escalate every four weeks to a final dose of 20 mg/kg/day during
a 16-week dose-escalation phase. Patients will be monitored for
physiological and biochemical markers of endothelial function. After 16
weeks, patients who show improvement in physiological or biochemical
markers of endothelial function and/or derive clinical benefit from 6R-BH4
will have the option to continue drug treatment for up to two years. During
this long-term treatment period, patients will also be monitored for sickle
cell crises and other vasoocclusive events which are the key problems
facing SCD patients.

The primary objective of this study is to evaluate the safety of oral
6R- BH4 administered in escalating doses in patients with sickle cell
disease. The secondary objective is to evaluate changes in physiological
and biochemical markers of endothelial function which underlie some key
aspects of SCD.

About 6R-BH4

6R-BH4, commonly known as BH4 or tetrahydrobiopterin, is a naturally
occurring enzyme cofactor that is required for numerous biochemical and
physiologic processes, including the synthesis of nitric oxide (NO). NO has
been shown to play a key protective role throughout the cardiovascular
system and produces multiple positive effects, such as relaxing smooth
muscle, reducing blood pressure, controlling inflammation and reducing
platelet aggregation. Researchers have demonstrated that a deficiency of
BH4 can disrupt NO synthesis, resulting in a loss of normal endothelial NO
production. This loss of endothelial NO production, commonly referred to as
endothelial dysfunction, has been associated with many cardiovascular
diseases, including diabetic vascular disease, peripheral arterial disease,
coronary arterial disease and pulmonary hypertension, and has been shown to
be a strong predictor of cardiovascular adverse events in a number of
clinical studies.

6R-BH4 is the same enzyme cofactor currently being evaluated in
BioMarin’s Kuvan(TM) (sapropterin dihydrochloride) for phenylketonuria
(PKU). In March 2006, BioMarin and Merck Serono (a division of Merck KGaA,
Darmstadt, Germany), BioMarin’s corporate partner for the Kuvan and 6R-BH4
programs, announced positive results from the Phase 3 clinical study of
Kuvan for PKU. All primary and secondary endpoints of the study were met.
The type and incidence of adverse events was similar in the Kuvan and
placebo groups. Kuvan was well tolerated and investigators reported that no
serious adverse event occurred.

About BioMarin

BioMarin develops and commercializes innovative biopharmaceuticals for
serious diseases and medical conditions. The company’s product portfolio is
comprised of two approved products and multiple clinical and preclinical
product candidates. Approved products include Naglazyme(R) (galsulfase) for
mucopolysaccharidosis VI (MPS VI), a product wholly developed and
commercialized by BioMarin, and Aldurazyme(R) (laronidase) for
mucopolysaccharidosis I (MPS I), a product which BioMarin developed through
a 50/50 joint venture with Genzyme Corporation. Investigational product
candidates include Kuvan(TM) (sapropterin dihydrochloride), a Phase 3
product candidate for the treatment of phenylketonuria (PKU), and 6R-BH4
for cardiovascular indications, which is currently in Phase 2 clinical
development for the treatment of peripheral arterial disease. For
additional information, please visit BMRN. Information on
BioMarin’s website is not incorporated by reference into this press
release.

Forward-Looking Statements

This press release contains forward-looking statements about the
business prospects of BioMarin Pharmaceutical Inc., including, without
limitation, statements about: the timing of BioMarin’s clinical trials of
6R-BH4 for sickle cell disease; the continued clinical development of
6R-BH4; expectation regarding regulatory filings for Kuvan; and actions by
regulatory authorities, including actions related to 6R-BH4. 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 preclinical studies and clinical trials
of 6R-BH4 for sickle cell disease; actions related to Kuvan; the content
and timing of decisions by the U.S. Food and Drug Administration, the
European Commission and other regulatory authorities concerning each of the
described product candidates; and those factors detailed in BioMarin’s
filings with the Securities and Exchange Commission, including, without
limitation, the factors contained under the caption “Risk Factors” in
BioMarin’s 2006 Annual Report on Form 10-K, as amended, and the factors
contained in BioMarin’s reports on Form 8-K. Stockholders are urged not to
place undue reliance on forward-looking statements, which speak only as of
the date hereof. BioMarin is under no obligation, and expressly disclaims
any obligation to update or alter any forward-looking statement, whether as
a result of new information, future events or otherwise.

BioMarin Pharmaceutical Inc.
bmrn

View drug information on Kuvan.