Exhibit 99.1
CONTACTS:
For BioMarin For Genzyme
Joshua Grass (investors) Sally Curley (investors)
(415) 884-6777 (617) 591-7140
Fredda Malkoff (media) Dan Quinn (media)
Feinstein Kean Healthcare (617) 591-5849
(617) 577-8110
For Immediate Release
April 30, 2003
BioMarin, Genzyme Announce FDA Marketing Approval for Aldurazyme
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New Enzyme Replacement Therapy Offers Hope to People with MPS I Novato, Ca.
and Cambridge, Ma.- BioMarin Pharmaceutical Inc. (Nasdaq and SWX: BMRN) and
Genzyme General (Nasdaq: GENZ) today announced that the U.S. Food and Drug
Administration (FDA) has granted marketing approval for
Aldurazyme(R)(laronidase), the first specific treatment approved for people with
mucopolysaccharidosis I (MPS I).
Aldurazyme is indicated for patients with the Hurler and Hurler-Scheie
forms of MPS I, and for Scheie patients with moderate to severe symptoms. The
risks and benefits of treating mildly affected patients with the Scheie form
have not been established. Aldurazyme has not been evaluated for effects on the
central nervous system manifestations of the disorder.
Clinical trials have demonstrated that Aldurazyme can provide clinically
important benefits for patients, including improved pulmonary function and
walking ability. Aldurazyme has also been shown to be effective at reducing the
excess carbohydrates that are stored in the organs of patients with MPS I,
providing evidence that the enzyme is effective at a biochemical level.
As the first drug ever approved for MPS I, Aldurazyme has been granted
orphan drug status in the United States, which confers seven years of market
exclusivity.
"We have observed remarkable improvements in the lives of patients after
treatment with Aldurazyme," said Joseph Muenzer, MD, PhD, Associate Professor of
Pediatrics, University of North Carolina, and a principal investigator for the
Aldurazyme clinical trials. "Prior to development of this enzyme replacement
therapy, physicians were limited primarily to managing the wide array of
symptoms in MPS I patients. Now, by addressing the underlying pathophysiology,
we have the opportunity to change the course of this disease for the better."
MPS I is a rare, progressive, debilitating disease caused by a deficiency
of the enzyme alpha L-iduronidase that affects an estimated 3,000 to 4,000
people worldwide, including approximately 1,000 in the United States. Patients
who lack this enzyme accumulate a carbohydrate called glycosaminoglycan (GAG) in
tissues and organ systems. A majority of patients die before adulthood due to a
wide range of problems related to the disease, including progressive damage to
the heart, lungs, liver, and kidneys.
Fredric Price, Chairman and Chief Executive Officer, BioMarin
Pharmaceutical Inc. said, "Approval of Aldurazyme marks a critical milestone in
the transformation of BioMarin to a commercially-focused organization. To have
taken a product from concept to approval in less than six years is a remarkable
developmental achievement and sets the stage for other products in our pipeline
of enzyme therapeutics. Given the serious, progressive nature of MPS I, we are
heartened by the FDA's rapid review of the application. We now look forward to
working with Genzyme to make Aldurazyme widely available to meet this important
unmet medical need."
Henri Termeer, Chairman and Chief Executive Officer, Genzyme Corporation
said, "We are proud to be able to bring Aldurazyme to individuals with MPS I in
the coming weeks. Patients and their families can expect the same high level of
care that we have helped to provide for others with rare genetic diseases,
including reimbursement and insurance information, disease information and
education, and connections to a strong network of health care professionals who
specialize in meeting the unique needs of patients with MPS I."
BioMarin and Genzyme have agreed with the FDA on a number of post-marketing
commitments. The companies will complete their previously announced study that
was initiated in December of 2002 to evaluate the safety and pharmacokinetics of
Aldurazyme in patients less than 5 years of age. In addition, they will conduct
an open-label dose optimization study in approximately 32 patients, and continue
the Phase 3 extension study for a total of 4 years from study initiation. In a
registry setting, the companies will also obtain long-term information related
to the natural history of MPS I and the safety and efficacy of Aldurazyme.
Marketing information
As specified in the companies' joint venture agreement, Aldurazyme will be
launched in the coming weeks in the United States by Genzyme, which will build
on more than a decade of experience in bringing enzyme replacement therapies to
patients with rare genetic diseases. The product will be manufactured at
BioMarin's plant in Novato, California, which has sufficient capacity to launch
the product and to meet worldwide commercial demand. Bulk enzyme will be sent to
Genzyme's manufacturing facility in Allston, Mass., or to a third-party facility
for the final filling and finish process.
In launching Aldurazyme, Genzyme will also offer LysoSolutionsSM, a network
of programs and services designed to support people living with MPS I and those
who care for them. Each program and service was developed to help optimize
patients' individual MPS I treatment programs by meeting specific patient and
medical needs.
In preparation for launch, Genzyme has forged strong alliances with the
National MPS Society and other patient support organizations, as well as leading
experts in the field of lysosomal storage disorders, pediatric groups,
geneticists, and other health care professionals involved in the
multidisciplinary management and treatment of individuals with MPS I.
Applications to market Aldurazyme are also pending in the European Union,
Canada, and Australia. In Europe, the Committee for Proprietary Medicinal
Products has issued a positive opinion on Aldurazyme, typically the final step
prior to marketing clearance for a drug in the 15 countries in the European
Union. A decision is expected by the European Commission in the second quarter
of 2003, and Canada and Australia are expected to act late this year or early
next year.
Clinical Trial Results
The companies completed two clinical trials with Aldurayzme, including a
26-week, 45-patient, randomized, double-blind, placebo-controlled study, during
which patients received 0.58 mg of Aldurazyme per kilogram of body weight
administered as a once-weekly infusion. That trial was followed by a 36-week
open label extension study. An earlier Phase 1 open label trial and extension
study enrolled 10 patients. Patients from the Phase 1 trials have been receiving
weekly Aldurazyme infusions for more than four years.
In each of these studies, Aldurazyme was shown to be effective at reducing
the glycosaminoglycan carbohydrates excreted in the urine, and at reducing liver
size, evidence suggesting that the enzyme is effective at a biochemical level.
The companies' Phase 3 study also demonstrated that treatment with
Aldurazyme improved lung function, as measured by change in percent predicted
Forced Vital Capacity (FVC), and increased endurance, as measured by the
distance covered in a six-minute walk test.
Patients demonstrated an improvement in FVC during the placebo-controlled
trial that was statistically significant in the Wilcoxon rank sum test (p=0.02)
and also statistically significant using an analysis of covariance (ANCOVA) to
adjust for baseline patient differences (p=0.007). The mean difference from
placebo was 4 percentage points. In patients receiving Aldurazyme who continued
into the extension study, a significant improvement from baseline was seen at 62
weeks (p=0.001). Respiratory problems are a major cause of morbidity and
mortality for individuals with MPS I.
Patients demonstrated an improvement in the six-minute walk test during the
placebo-controlled trial that approached statistical significance in the
Wilcoxon rank sum test (p=0.066) and was statistically significant using ANCOVA
to adjust for baseline heterogeneity (p=0.039). The mean difference from placebo
was 38 meters. In patients receiving Aldurazyme who continued into the extension
study, a significant improvement was seen at 62 weeks vs. baseline (p=0.005).
The clinical importance of the six-minute walk test derives from the fact that
impaired mobility is a significant and common disability for patients with MPS
I.
A positive trend toward improvement in sleep apnea was seen in the total
Aldurayzme study group (p=0.145), half of whom had sleep apnea at baseline.
Significant improvement (9 events/hour mean difference vs. placebo) was
demonstrated in a post-hoc analysis of patients who presented with sleep apnea
at baseline (p=0.037).
The most common adverse reactions associated with Aldurazyme treatment in
the clinical studies were upper respiratory tract infection, rash, and injection
site reaction. The most common adverse reactions requiring intervention were
infusion-related hypersensitivity reactions, including flushing, fever,
headache, and rash.
The most serious adverse reaction reported with Aldurazyme was an
anaphylactoid reaction which occurred in one patient approximately three hours
after the start of the infusion. The reaction consisted of urticaria and airway
obstruction, requiring tracheostomy. Preexisting MPS I-related upper airway
obstruction may have contributed to the severity of this reaction.
Approximately 91 percent of patients treated with Aldurazyme were positive
for antibodies to laronidase. The clinical significance of antibodies to
Aldurazyme is not known, including the potential for product neutralization.
There are no known contraindications to the use of Aldurazyme.
Genzyme General develops and markets therapeutic products and diagnostic
products and services. Genzyme General has six therapeutic products on the
market and a strong pipeline of therapeutic products in development focused on
the treatment of genetic diseases and other chronic debilitating disorders with
well-defined patient populations. Genzyme General is a division of Genzyme Corp.
BioMarin Pharmaceutical specializes in the development and
commercialization of therapeutic enzyme products to treat serious,
life-threatening diseases and conditions.
This press release contains forward-looking statements, including without
limitation statements about: market exclusivity for Aldurazyme; estimates
concerning the MPS I patient population; expectations and plans related to the
commercialization and manufacture of Aldurazyme, including the anticipated
timing of product launch; anticipated timing of decisions by regulatory
authorities in the European Union, Canada and Australia regarding marketing
applications for Aldurazyme; and expectations concerning BioMarin's other enzyme
therapeutics. These statements are subject to risks and uncertainties that could
cause actual results to differ materially from those projected in these
forward-looking statements. These risks and uncertainties include, among others:
the timing and content of decisions by regulatory authorities regarding other
products and exceptions to Orphan Drug market exclusivity; the ability to
establish and maintain relationships with third party distributors and
fill/finish facilities; the actual impact of the Committee for Proprietary
Medicinal Products' opinion on decisions made by the European Commission
regarding Aldurazyme; the content and actual timing of decisions by the European
Commission and other regulatory authorities concerning marketing applications
and labeling for Aldurazyme and manufacturing facilities to be used for
Aldurazyme; the safety and efficacy data obtained from commercial scale use of
Aldurazyme; the results of the ongoing safety and pharmacokinetics study and the
planned dose optimization study of Aldurazyme; the nature of long-term data
collected through a registry setting; the ability to manufacture sufficient
quantities of product and to do so in a timely and cost efficient manner; the
continued funding and operation of the joint venture between Genzyme and
BioMarin; decisions made by physicians, patients and third party payers
regarding the use of and reimbursement for Aldurazyme; the companies' ability to
obtain and maintain adequate patent and other proprietary rights protection for
Aldurazyme; the scope, validity and enforceability of patents and other
proprietary rights held by third parties related to therapies for MPS I and the
actual impact of such patents and other rights on the companies' ability to
commercialize Aldurazyme; the effectiveness of the companies' commercialization
plan for Aldurazyme; the accuracy of the companies' information concerning the
MPS I patient population and the competitive environment; and the risks and
uncertainties described in reports filed by Genzyme and BioMarin with the
Securities and Exchange Commission under the Securities Exchange Act of 1934, as
amended, including without limitation the factors contained under the caption
"Factors Affecting Future Operating Results" in Exhibit 99.2 to Genzyme
Corporation's 2002 Annual Report on Form 10-K as amended. Genzyme General
Division common stock is a series of common stock of Genzyme Corporation.
Therefore, holders of Genzyme General Division common stock are subject to all
of the risks and uncertainties described in Genzyme Corporation reports. Genzyme
and BioMarin caution investors not to place undue reliance on the
forward-looking statements contained in this press release. These statements
speak only as of the date of this press release, and Genzyme and BioMarin
undertake no obligation to update or revise the statements.
Genzyme(R) is a registered trademark and LysoSolutionsSM is a service mark
of Genzyme Corporation. Aldurazyme(R) is a registered trademark of
BioMarin/Genzyme LLC. All rights reserved.
BioMarin's press releases and other company information is available at
http://www.biomarinpharm.com. Information on BioMarin's website is not
incorporated by reference into this press release.
A photo of Aldurazyme is available at the following site on the Internet:
ftp://ftp.genzyme.com/communications/aldurazyme.