NOVATO, California, and GENEVA, Switzerland, September 12
/PRNewswire-FirstCall/ -- BioMarin Pharmaceutical Inc. (Nasdaq: BMRN , SWX:
BMRN) and Serono (virt-x: SEO and NYSE: SRA) today announced data from
clinical studies of Phenoptin(TM) (sapropterin dihydrochloride), an
investigational oral small-molecule therapeutic for the treatment of
phenylketonuria (PKU), that will presented at the 56th Annual Meeting of
the American Society of Human Genetics (ASHG) being held in New Orleans,
Louisiana, October 9 to 13, 2006. Data to be presented is summarized below.
    ASHG Program # 57: Phase 3 Clinical Study of Phenoptin for PKU
    Results from the Phase 3, double-blind, placebo-controlled clinical
study of Phenoptin (commonly referred to as 6R-BH4, or BH4) in patients
with elevated blood phenylalanine (Phe) levels demonstrated a statistically
significant reduction at six weeks in blood Phe levels (p<0.0001) in
patients receiving 10 mg/kg/day of Phenoptin, compared with those receiving
placebo. 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. A summary of
the data from this trial was previously announced in a press release issued
March 15, 2006. Following the six-week, double-blind study, patients were
enrolled into a 22-week, Phase 3 open-label extension study, which is
currently ongoing. This study is designed to further evaluate the long-term
safety and efficacy of Phenoptin, as well as dose titration.
    These data will be presented by Harvey Levy, M.D., of Children's
Hospital of Boston, Boston, Massachusetts, in an oral presentation
scheduled for October 11, 2006.
    ASHG Program # 2332/C : Phase 2 Screening Study of Phenoptin for PKU
    Results from the Phase 2 screening study conducted to identify
appropriate patients for inclusion in the Phase 3, double-blind,
placebo-controlled study of PKU, demonstrate that Phenoptin was well
tolerated and rapidly reduced blood Phe levels by varying degrees in PKU
patients across the complete spectrum of PKU phenotypes. The majority of
adverse events were mild, including headaches and gastrointestinal
disorders, and all were resolved without complications and none were
assessed as clinically significant.
    A total of 490 patients, age 8 or older, with blood Phe levels of at
least 450microM were screened to determine eligibility for inclusion into
the Phase 3 study. Patients who demonstrated a 30 percent or greater
reduction in blood Phe level from baseline following an 8-day course of 10
mg/kg per day of Phenoptin were eligible to enroll into the Phase 3 study.
Of the 485 patients who completed the 8-day treatment course, 96
demonstrated at least a 30 percent reduction in blood Phe. The data from
the Phase 2 screening study are summarized in the table below:
    Baseline Phe Level      Number of Patients with 30% Reduction in
    (microM)                Blood Phe Following 8 days of Treatment
                            with 10mg/kg/day of Phenoptin[1]
    450 to 600              31 of 57 (54.4%)
    600 to 900              38 of 157 (24.2%)
    900 to 1200             14 of 135 (10.4%)
    >1200                   13 of 136 (9.6%)
    These data will be presented by Barbara Burton, M.D., of Children's
Memorial Hospital, Northwestern University Feinberg School of Medicine,
Chicago, Illinois, at a poster session scheduled for October 12, 2006.
    These results are consistent with the estimated 30 percent to 50
percent frequency of BH4-responsiveness in the overall PKU population based
on the retrospective analysis conducted by Bernegger and Blau (Mol Genet
Metab. 2002 Dec;77(4):304-13), given the following considerations: [2]
    - The Phase 2 screening study evaluated Phenoptin dosed at 10 mg/kg,
half the dose administered to patients included in the retrospective
analysis conducted by Bernegger and Blau. Data from a prior study conducted
by Matalon, et.al., (Mol Genet Metab. 2005 Dec;86 Suppl 1:S17-21)
demonstrate that BH4 dosed at 20mg/kg results in a greater number of BH4
responders than BH4 dosed at 10mg/kg.
    - The Phase 2 study, due to minimum blood Phe level requirements, was
biased toward individuals with the more severe form of PKU who are less
likely to demonstrate a response to BH4.
    ASHG Program # 1415/A: Meta-Analysis Evaluating Blood Phe Levels and
Clinical Outcomes in PKU
    Results from a BioMarin-sponsored meta-analysis conducted to determine
if blood Phe levels can be used as a predictive biomarker of clinical
outcomes for the development of new PKU treatments confirm findings from
previous studies reporting a significant correlation between concurrent and
long-term blood Phe levels and intelligence quotient (IQ) in individuals
with PKU. Researchers conducted a comprehensive formal protocol-driven
analysis that evaluated data (published from 1980 to 2004) that related Phe
level to IQ. The key findings of this analysis are as follows:
    - each 100microM increase in blood Phe in the range of 423microM to
750microM is correlated with a 1.3 to 3.1 reduction in IQ for people with
PKU 0 to 12 years of age;
    - each 100 microM increase in Phe in a range of 394microM to 666microM
is correlated to a 1.9 to 4.1 point decrease in IQ for lifetime exposure;
    - the meta-analysis study also confirmed that the majority of PKU
patients do not comply with the recommended low-Phe diet, leading to blood
Phe levels that exceed recommended maximum levels.
    These data will be presented by Susan Waisbren, Ph.D., of Children's
Hospital of Boston, Boston, Massachusetts, at a poster session scheduled
for October 10, 2006.
    References
    1. The data in this press release reflect information that will be
presented in the poster presentation at the ASHG annual meeting being held
in October.
    2. The following is a summary of the data published in Molecular
Genetics and Metabolism (Mol Genet Metab. 2002 Dec;77(4):304-13.) regarding
6R-BH4 responsiveness in 278 newly diagnosed PKU patients:
    Baseline Phe Level      Percent of Patients with 30%
    (microM)                Reduction following 8 days of
                            Treatment with 20mg/kg/day of
                            6R-BH4
    400 to 800              74%
    800 to 1200             33%
    1200 to 1600            17%
    1600 to 2200            0%
    >2200                   10%


    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.
    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 Phenoptin(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 poorly controlled hypertension. For
additional information, please visit http://www.BMRN.com. Information on
BioMarin's website is not incorporated by reference into this press
release. The websites indicated in this press release are provided by
BioMarin as additional information for interested parties. With the
exception of its own websites, BioMarin does not endorse any particular
organization or the content contained on their website.
    Naglazyme(R) is a registered trademark of BioMarin Pharmaceutical Inc.
    Aldurazyme(R) is a registered trademark of BioMarin/Genzyme LLC.
    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.
    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 expected market for 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; 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 any government
investigations and litigation. Serono is providing this information as of
the date of this press release, and 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.

Link to this page: