All Primary and Secondary Endpoints Met

    BioMarin to Hold Conference Call and Webcast Today at 4:30 p.m. ET (22:30
CET)

    NOVATO, California, and GENEVA, Switzerland, March 15
/PRNewswire-FirstCall/ -- BioMarin Pharmaceutical Inc. (Nasdaq and SWX: BMRN)
and Serono (virt-x: SEO and NYSE: SRA) announced today positive results of a
Phase 3, double-blind, placebo-controlled clinical study of Phenoptin(TM)
(sapropterin dihydrochloride), an investigational oral small molecule for the
treatment of phenylketonuria (PKU). Results confirm that all pre-specified
primary and secondary endpoints were met and data from the Phase 3 study
demonstrate a statistically significant reduction at six weeks in blood
phenylalanine (Phe) levels (p<0.0001) in patients receiving Phenoptin,
compared with those receiving placebo.
    Emil Kakkis, M.D., Ph.D., Chief Medical Officer of BioMarin stated, "This
is an exciting day for PKU patients worldwide as a simple oral treatment that
could potentially help them reach their treatment goals is now one step
closer to becoming a reality. For many patients with genetic diseases, not
enough has been done to push forward important new treatments, and we are
particularly happy to be able to collaborate with the numerous clinicians and
investigators worldwide who have worked on tetrahydrobiopterin and transform
their hard work into what could become the first approved drug therapy for
this disease."
    Susan Herbert, Ph.D., Corporate Vice President, Head of Reproductive
Health and Metabolic Endocrinology Global Product Development at Serono
commented, "These encouraging results represent an important milestone in
Serono's strategy to bring to market novel treatments for serious metabolic
diseases. PKU is a rare condition that can be severely debilitating.
Phenoptin has the potential to offer patients hope for the successful,
long-term management of this disease."
    The study enrolled 89 patients with elevated blood Phe levels aged eight
years and above at 29 sites in the United States, Europe and Canada. All
patients had demonstrated a reduction in blood Phe levels (approximately 30
percent or more) following treatment with Phenoptin in a Phase 2 screening
study.
    The patients were randomly assigned to receive placebo or 10 mg/kg of
Phenoptin daily for six weeks. Patients were evaluated every two weeks for
changes in blood Phe levels and adverse events. The primary endpoint of the
study was the difference in mean blood Phe levels between the placebo and
Phenoptin groups at Week 6, adjusted for baseline levels. A total of 87
patients completed six weeks of treatment.
    Following the six-week double-blind study, patients were eligible to
enroll into an on-going 22 week Phase 3 open-label extension study designed
to further evaluate the long-term safety and efficacy of Phenoptin, as well
as dose titration. BioMarin and Serono expect to file marketing authorization
applications for Phenoptin for PKU in the United States and European Union in
2007. BioMarin has licensed to Serono exclusive rights for Phenoptin outside
of the United States and Japan.
    Results from the Phase 3 double-blind study are summarized below:
    Primary Endpoint
    - Patients treated with Phenoptin for six weeks had a mean decrease in
blood Phe level of 236 mM (29 percent) compared to a mean increase of 3 mM (3
percent) in the placebo group (p<0.0001). Prior to treatment, patients in the
Phenoptin group and placebo group had mean blood Phe levels of 843 mM and 888
mM, respectively.
    Secondary Endpoints
    - At Week 6, the percentage of patients in the Phenoptin group with blood
Phe levels less than or equal to 600 mM was 54 percent compared to 23 percent
in the placebo group (p=0.004). At baseline the proportions were 17 percent
and 19 percent for the Phenoptin and placebo groups, respectively.
    - The mean blood Phe level at each visit among patients receiving
Phenoptin showed a consistent reduction compared to the blood Phe levels in
patients receiving placebo (p<0.001) throughout the six-week period.
    - The type and incidence of adverse events was similar in the Phenoptin
and placebo groups. Phenoptin was well tolerated and investigators reported
that no serious adverse event occurred.
    About Phenoptin
    Phenoptin is an investigational oral small molecule therapeutic for the
treatment of PKU. The active ingredient in Phenoptin, 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. Preliminary clinical data
have suggested that Phenoptin has a potential to produce significant
reductions in blood Phe levels in the subset of patients who are
BH4-responsive. BioMarin and Serono estimate that Phenoptin could be a
potential treatment option for approximately 30 percent to 50 percent of the
estimated 50,000 individuals in the developed world who have been diagnosed
with PKU.
    Phenoptin received orphan drug designation to treat PKU from both the
U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMEA).
If Phenoptin becomes the first drug therapy approved for the treatment of
PKU, Phenoptin would receive seven years of market exclusivity in the United
States and 10 years in the European Union for this indication. Additionally,
the FDA has granted Phenoptin Fast Track designation, which is designed to
facilitate the development and expedite the review of new drugs that are
intended to treat serious or life-threatening conditions and that demonstrate
the potential to address unmet medical needs.
    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 (Phe),
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 brain, resulting in a variety of complications
including severe mental retardation and brain damage, mental illness,
seizures and tremors, and cognitive problems. As a result of global newborn
screening efforts implemented in the 1960s and early 1970s, virtually all PKU
patients in developed countries have been diagnosed at birth. The only
treatment currently available for PKU patients is a highly restrictive and
expensive medical food diet that most patients fail to adhere to the extent
needed for achieving adequate control of blood Phe levels. To learn more
about PKU, please visit http://www.PKU.com. Information on this website is not
incorporated by reference into this press release.
    Conference Call and Webcast Scheduled for Today, March 15 at 4:30 p.m. ET
(22:30 CET)
    BioMarin will host a conference call and webcast to discuss today's
announcement. This event can be accessed on the investor section of the
BioMarin website at http://www.BMRN.com.
    Date: March 15, 2006
    Time: 4:30 p.m. ET (22:30 CET)
    U.S. & Canada Toll-free Dial in #: 800-299-0148
    International Dial in #: +1-617-801-9711
    Participant Code: 44460826
    Replay Toll-free Dial in #: 888-286-8010
    Replay International Dial in #: +1-617-801-6888
    Replay Code: 56350669
    About BioMarin
    BioMarin develops and commercializes innovative biopharmaceuticals for
serious diseases and medical conditions. The company's product portfolio is
comprised of three approved products and multiple clinical and preclinical
product candidates. Approved products include Naglazyme(TM) (galsulfase) for
mucopolysaccharidosis VI (MPS VI), a product wholly developed and
commercialized by BioMarin, Aldurazyme(R) (laronidase) for
mucopolysaccharidosis I (MPS I), and Orapred(R) (prednisolone sodium
phosphate oral solution) for inflammatory conditions. Investigational product
candidates include Phenoptin(TM) (sapropterin dihydrochloride), a Phase 3
product candidate for the treatment of phenylketonuria (PKU). For additional
information, please visit http://www.BMRN.com. Information on BioMarin's website is
not incorporated by reference into this press release.
    Aldurazyme(R) is a registered trademark of BioMarin/Genzyme LLC.
    Orapred(R) is a registered trademark of Medicis Pediatrics, Inc., and is
used under license.
    About Serono
    Serono is a global biotechnology leader. The Company has eight
biotechnology products, Rebif(R), Gonal-f(R), Luveris(R), Ovidrel(R)
/Ovitrelle(R), Serostim(R), Saizen(R), Zorbtive(TM) and Raptiva(R). In
addition to being the world leader in reproductive health, Serono has strong
market positions in neurology, metabolism and growth and has recently entered
the psoriasis area. The Company's research programs are focused on growing
these businesses and on establishing new therapeutic areas, including
oncology and autoimmune diseases. Currently, there are more than 25 on-going
development projects.
    In 2005, Serono, whose products are sold in over 90 countries, achieved
worldwide revenues of US$2,586.4 million. Reported net loss in 2005 was
US$106.1 million, reflecting a charge of US$725 million taken relating to the
settlement of the US Attorney's Office investigation of Serostim. Excluding
this charge as well as other non-recurring items, adjusted net income grew
28.4% to US$565.3 million in 2005. Bearer shares of Serono S.A., the holding
company, are traded on the virt-x (SEO) and its American Depositary Shares
are traded on the New York Stock Exchange (SRA).
    Background Material
    For free B-roll, video and other content for Serono and its products,
please visit the Serono Media Center http://www.thenewsmarket.com/Serono. You can
download print-quality images and receive broadcast-standard video digitally
or by tape from this site. Registration and video is free to the media.
    Forward-Looking Statements
    For BioMarin
    This press release contains forward-looking statements about the business
prospects of BioMarin Pharmaceutical Inc., including, without limitation,
statements about: the development of its product candidate Phenoptin; the
final results of the data from the Phase 3 trial of Phenoptin; and
expectations regarding filings with regulatory agencies. 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: the results
of preclinical and clinical trials related to Phenoptin; results and timing
of current and planned clinical trials of Phenoptin for the treatment of PKU;
the content and timing of decisions by the U.S. Food and Drug Administration,
the European Medicines Agency and other regulatory authorities concerning
Phenoptin; the conclusion of the final data analysis of the Phase 3 trial of
Phenoptin; 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 2005 Annual
Report on Form 10-K and the factors contained in BioMarin's reports on Forms
10-Q and 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 statements.
    For Serono
    Some of the statements in this press release are forward looking. Such
statements are inherently subject to known and unknown risks, uncertainties
and other factors that may cause actual results, performance or achievements
of Serono S.A. and affiliates to be materially different from those expected
or anticipated in the forward-looking statements. Forward-looking statements
are based on Serono's current expectations and assumptions, which may be
affected by a number of factors, including those discussed in this press
release and more fully described in Serono's Annual Report on Form 20-F filed
with the U.S. Securities and Exchange Commission on February 28, 2006. These
factors include any failure or delay in Serono's ability to develop new
products, any failure to receive anticipated regulatory approvals, any
problems in commercializing current products as a result of competition or
other factors, our ability to obtain reimbursement coverage for our products,
the outcome of government investigations and litigation and government
regulations limiting our ability to sell our products. Serono has no
responsibility to update the forward-looking statements contained in this
press release to reflect events or circumstances occurring after the date of
this press release.

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