Exhibit 99.1
Contacts:
Joshua A. Grass Susan Ferris
Manager, Investor Relations Manager, Corporate Communications
BioMarin Pharmaceutical Inc. BioMarin Pharmaceutical Inc.
(415) 506-6777 (415) 506-6701
For Immediate Release:
BioMarin Presents Positive Long-Term Results from Ongoing Phase 1 and Phase 2
Clinical Studies of Aryplase for MPS VI
BioMarin on Track to File for US and EU Marketing Authorization in 2004 Pending
Positive Results from the Ongoing Phase 3 Study
Novato, CA, November 6, 2003 - BioMarin Pharmaceutical Inc. (Nasdaq and SWX:
BMRN) announced positive long-term results from Phase 1 and Phase 2 clinical
studies of Aryplase(TM), an investigational enzyme replacement therapy for the
treatment of mucopolysaccharidosis VI (MPS VI). Long-term data from both studies
indicate that Aryplase is generally well-tolerated and that patients continue to
benefit from Aryplase treatment.
Data from the Phase 1 and Phase 2 studies are being presented by John Hopwood,
Ph.D., of Brigham and Women's Hospital, Adelaide, Australia, and by Paul
Harmatz, M.D., of Children's Hospital Research Institute, Oakland, California,
respectively, at the 53rd Annual Meeting of the American Society of Human
Genetics in Los Angeles, California, November 4-8, 2003.
"We are pleased to see the clinical improvements these patients experienced,
especially those observed beyond the initial six months of treatment and well
into the second year of weekly Aryplase infusions," stated Stuart Swiedler,
M.D., Ph.D., Vice President, Clinical Affairs of BioMarin. "Already, well in
advance of a potential NDA filing, we have enrolled approximately 170 MPS VI
patients in clinical and disease survey studies, whom someday may benefit from
Aryplase treatment."
Phase 2 Study
The Phase 2 open-label study enrolled 10 patients with MPS VI at a dose of 1.0
mg/kg, the higher of two doses investigated in the Phase 1 dose-ranging study.
The study enrolled patients at two sites, one in the United States (US) and one
in Australia. Results after 48 weeks of treatment with Aryplase are summarized
below:
o Endurance as measured by distance walked in 12 minutes improved by an
average of 139 percent (211 meters) over the baseline distance. This
represents an average incremental improvement of 56 meters over the
improvement observed after 24 weeks of Aryplase treatment. The
12-minute walk test is the primary endpoint in the current Phase 3
clinical study of Aryplase.
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o Endurance as measured by the number of stairs climbed in three minutes
increased by an average of 147 percent (61 stairs) over the baseline
number. This represents an average incremental improvement of an
additional 13 stairs over the improvement observed after 24 weeks of
Aryplase treatment. The 3-minute stair climb is a secondary endpoint in
the current Phase 3 study.
o Urinary glycosaminoglycan (GAG) level, another secondary endpoint in
the current Phase 3 study, was reduced by 76 percent on average after
48 weeks of treatment with Aryplase. Urinary GAG level was reduced by
71 percent on average after 24 weeks of treatment with Aryplase. GAG,
the carbohydrate residue that accumulates in tissues of patients and
causes MPS VI disease, is a biomarker for enzyme activity in vivo.
o Sustained improvements were also observed in joint pain and stiffness,
and variable improvements were observed in joint range of motion.
Reduction in liver and spleen size was observed in all five patients
presenting with hepatosplenomegally at baseline, and four of the five
now have liver volumes in the normal range. Pulmonary function
improvements were observed in several patients, primarily between 24
and 48 weeks.
Phase 1 Study
The randomized, double-blind, Phase 1 study initially investigated two doses of
Aryplase (0.2 mg/kg and 1.0 mg/kg) in two groups of three patients each.
Following positive results after 24 weeks of treatment, all six patients
continued to receive treatment at 1.0 mg/kg in an open-label extension study.
Results after 96 weeks of treatment are summarized below:
o Endurance as measured by the distance walked in six minutes improved by
an average of 96 percent (120 meters) over baseline after 96 weeks of
therapy. Gains in the 6-minute walk test were maintained or improved
from week 48 to week 96 for the four evaluable patients in the study at
the 96-week time point.
o Urinary GAG level was reduced by 75 percent on average after 96 weeks
of treatment. Patients who initially received the lower of the two
doses experienced an incremental decrease in GAG level after receiving
treatment with the higher dose.
Phase 1 and Phase 2 Safety
Aryplase was generally well-tolerated during both clinical studies. In the Phase
1 study, after nearly two years of treatment during which patients underwent 508
infusions, there was one serious adverse event (SAE) that the investigator
attributed as related to drug. This patient experienced urticaria (rash)
approximately three hours after the start of the week 76 infusion. After the
rate of infusion was decreased, the patient recovered. There were 46 mild, four
moderate, and no severe drug-related adverse events (AE). Fever and dermatitis
were most commonly observed. In the Phase 2 study, out of 475 infusions, there
was one SAE, an asthma attack, which the investigator attributed as possibly
related to drug. A total of 31 infusion-related AEs were attributable to the
drug, 18 of which were mild skin hypersensitivity reactions in one patient, and
four similar incidences in a second patient. Most patients in both studies
developed antibodies to Aryplase although antibody presence did not correlate
with clinical safety or efficacy. Additionally, approximately 1.5 years after
initiating treatment, relative antibody levels for all patients involved in the
Phase 1 study fell to levels slightly above background.
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BioMarin has received orphan drug and fast track designations for Aryplase from
the US Food and Drug Administration (FDA). In addition, the European Commission
has designated Aryplase for the treatment of MPS VI as an orphan medicinal
product in the European Union (EU). BioMarin is currently conducting a
multinational, placebo-controlled, double-blind, Phase 3 study of Aryplase in
patients with MPS VI. The company expects to announce data from this study in
the second quarter of 2004, and pending positive data, to file for marketing
authorization in the US and EU in the fourth quarter of 2004.
About MPS VI
MPS VI (also known as Maroteaux-Lamy Syndrome) is a debilitating,
life-threatening genetic disease for which no drug therapies are currently
available. MPS VI is caused by a deficiency of the enzyme arylsulfatase B. The
deficiency leads to the accumulation of GAG in the lysosomes, the digestive
organelles of the cell, giving rise to progressive cellular, tissue and organ
system dysfunction. Debilitating symptoms can include impaired cardiac and
pulmonary function, delayed physical development, skeletal and joint
deformities, impaired vision and hearing, sleep apnea, and reduced endurance.
The majority of subjects die from disease-related complications between
childhood and early adulthood, depending on the severity of the disease.
To date, BioMarin has enrolled approximately 170 patients in its Phase 1, Phase
2, Phase 3 and disease survey studies. BioMarin estimates that there are
approximately 1,100 MPS VI patients in the developed world, an estimate based on
published epidemiological data.
BioMarin Pharmaceutical Inc. specializes in the development and
commercialization of enzyme therapies for serious, life- threatening diseases
and conditions.
Forward-Looking Statement
This press release contains forward-looking statements about the business
prospects of BioMarin Pharmaceutical Inc., including without limitation,
statements about: the presentations about clinical data related to Aryplase;
expected timing of ongoing clinical trials for Aryplase; patient registry
activities; and actions by regulatory authorities. 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 extension
studies and clinical trials; the content and timing of decisions by the FDA, the
European Commission
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and other regulatory authorities concerning Aryplase; and those factors detailed
in BioMarin's filings with the Securities and Exchange Commission, including,
without limitation, the factors contained under the caption "Factors That May
Affect Future Results" in BioMarin's 2002 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 statement,
whether as a result of new information, future events or otherwise.
BioMarin's press releases and other company information are available online at
http://www.BMRN.com. Information on our website is not incorporated by
reference into this press release.
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