EXHIBIT 99.1
Contacts:
For BioMarin: For Genzyme:
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Jeremy Price Dan Quinn (media)
Manager, Investor Relations (617) 591-5849
BioMarin Pharmaceutical Inc.
(415) 884-6777
Fredda Malkoff Elliott Hillback (investors)
Feinstein Kean Healthcare (617) 252-7842
(617) 577-8110
For Immediate Release:
BioMarin and Genzyme Announce Positive Findings
from Phase 3 Trial and Extension Study of Aldurazyme for MPS I
Novato, CA and Cambridge, MA, June 24, 2002 - BioMarin Pharmaceutical Inc.
(Nasdaq and Swiss SWX New Market: BMRN) and Genzyme General (Nasdaq: GENZ) today
announced detailed results from the six-month double-blind Phase 3 clinical
trial of Aldurazyme(TM) (laronidase) and preliminary six-month findings from the
trial's ongoing open-label extension study. Aldurazyme is an investigational
enzyme replacement therapy for patients with mucopolysaccharidosis I (MPS I).
Data from the extension study indicate that patients who received Aldurazyme for
twelve months continued to improve upon the results seen in the first six months
of treatment.
Ed Wraith, M.D., of the Willink Biochemical Genetics Unit at the Royal
Manchester Children's Hospital, Manchester, UK, and one of the trial's clinical
investigators, presented findings from both the double-blind and extension study
portions of the Phase 3 trial on Saturday, June 22 at the International
Symposium on Mucopolysaccharide and Related Diseases in Paris, France. BioMarin
and Genzyme will submit the six-month interim extension study data to the U.S.
Food and Drug Administration (FDA) in the third quarter to complete their
"rolling" Biologics License Application (BLA).
"The data presented on Saturday indicate that this is a promising treatment for
the complex array of symptoms experienced by MPS I patients, who currently have
no specific treatment available to them," said Dr. Wraith. "I am particularly
encouraged by the results seen in patients who have now been on treatment for a
full year."
Extension Study Results
All 45 MPS I patients from the six-month, randomized, double-blind,
placebo-controlled Phase 3 trial were enrolled in the open-label extension study
in order to further evaluate the safety and efficacy of Aldurazyme. Patients who
were previously on placebo were switched to Aldurazyme for the extension study,
while those patients who received Aldurazyme during the first six months of the
trial continued to receive Aldurazyme via weekly infusions in the extension
study.
The extension study includes analysis of the same two primary endpoints that
were evaluated in the double-blind portion of the Phase 3 trial: pulmonary
function, as measured by forced vital capacity (FVC), and endurance, as measured
by the distance covered in a six-minute walk test. Patients who received
Aldurazyme in the double-blind portion of the trial and who continue to receive
treatment in the extension study maintained improvement in FVC, moving from a
5.3 percentage point mean increase in percent of predicted normal FVC during the
first six months of treatment to a 5.9 percentage point mean increase after an
additional six months of treatment as part of the extension study. These same
patients improved from a 19.7 meter mean increase in the six-minute walk test
over the first six months of treatment to a 42.9 meter mean increase after six
additional months of treatment as part of the extension study.
During the extension study, patients who were switched from placebo to
Aldurazyme experienced a slight decline in FVC compared to baseline (-0.6%) but
began to improve during the second half of the six-month extension period. In
the six-minute walk test, patients who were switched from placebo to Aldurazyme
showed a mean improvement of 23.8 meters, which is consistent with the increase
seen among patients who received six months of treatment with Aldurazyme during
the double-blind portion of the trial.
Additional findings from the extension study have been generally consistent with
results seen in both the Phase 1 trial and the double-blind portion of the Phase
3 trial: statistically significant reductions in liver size and in the excretion
of urinary glycosaminoglycans (GAGs), the carbohydrate substances that
accumulate in patients with MPS I. Patients who received Aldurazyme in both the
double-blind and extension study periods maintained the reductions in liver size
and urinary GAG excretion that were seen in the first six months of treatment.
The safety profile in the extension study has been comparable to the
double-blind period. The most commonly reported reactions were fever, headache,
rhinitis, and rash. One patient in the extension study died of causes considered
by the principal investigator to be unrelated to treatment.
Double-Blind Phase 3 Results
In addition to the extension study data, Dr. Wraith presented a comprehensive
review of data from the double-blind portion of the Phase 3 trial, from which
preliminary results were announced last November. In the first six months of the
trial, patients treated with Aldurazyme achieved a 5.3 percentage point mean
increase in pulmonary capacity as measured by FVC compared to patients treated
with placebo (p=0.016). In November, BioMarin and Genzyme reported a p-value of
0.028 for the FVC test, but subsequent analysis led to the revision to 0.016. In
addition, patients demonstrated a positive trend in endurance as measured by a
six-minute walk test, where they improved by a mean of 38.1 meters compared to
patients treated with placebo (p=0.066). When analyzed by a prospectively
defined parametric statistical analysis that accounts for pre-existing
differences in individual patients, the six-minute walk test reached statistical
significance (p=0.039).
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Patients in the Aldurazyme group achieved statistically significant mean
reductions in liver size (p=0.001) and urinary GAG excretion (p<0.001),
consistent with the findings in the Phase 1 trial.
The sleep study, as measured by the apnea-hypopnea index, showed a positive
trend (p=0.145) in the overall patient population. One post-hoc subset analysis
of the 21 patients judged by the investigators to have clinically significant
sleep apnea at baseline demonstrated a statistically significant improvement
(p=0.037). Two additional secondary endpoints did not reach statistical
significance: a health assessment questionnaire and shoulder range of motion.
The safety profile in the double-blind portion of the Phase 3 trial was
comparable between the treatment group and the placebo group, with no
Aldurazyme-related serious adverse events. The most commonly reported reactions
were fever (14 patients on the placebo and 10 in the treatment group); headache
(16 on placebo and 11 in the treatment group); rhinitis (10 on placebo and 8 in
the treatment group); and rash (5 on placebo and 8 in the treatment group).
On Friday, June 21, Joseph Muenzer, M.D., Ph.D., Associate Professor of
Pediatrics at the University of North Carolina, Chapel Hill, and also one of the
clinical trial's investigators, presented new perspectives on the burden of
illness among MPS I patients, which were derived from baseline evaluations of
the 45 patients enrolled in the Phase 3 trial of Aldurazyme. Dr. Muenzer's
analysis highlights the heterogeneity of the clinical effects of MPS I, which
include organ damage, particularly to the liver and spleen, respiratory
problems, musculoskeletal disorders, a high rate of infections, and
gastrointestinal problems.
About MPS I
MPS I (also known as Hurler, Hurler-Scheie, and Scheie syndromes) is a
life-threatening genetic disease caused by a deficiency of the enzyme
alpha-L-iduronidase. This deficiency leads to the accumulation of complex
carbohydrates (GAGs) in the lysosomes of cells, leading to the progressive
dysfunction of cellular, tissue and organ systems. Resulting symptoms can
include impaired cardiac and pulmonary function, delayed physical development,
skeletal and joint deformities, reduced endurance, and in some cases, delayed
mental function. A majority of patients die before adulthood from complications
of the disease.
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BioMarin and Genzyme formed a joint venture in 1998 to develop and commercialize
Aldurazyme worldwide. Under the terms of the joint venture, if approved for
commercial sale, BioMarin will manufacture Aldurazyme and Genzyme will have
responsibility for the commercialization of the product. The companies have
obtained Orphan Drug designation and Fast Track status for Aldurazyme for MPS I
from the FDA and orphan medicinal product designation from the European Agency
for the Evaluation of Medicinal Products (EMEA).
Genzyme General develops and markets therapeutic products and diagnostic
products and services. Genzyme General has five 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: the results from the six-month findings of the open
label extension study (which may differ from the preliminary results reported in
this press release), the expected timing of completion of the BLA filing for
Aldurazyme, and the potential regulatory approval for the commercialization of
Aldurazyme and commercialization plans. 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 results and timing of the on-going
Phase 3 trial; the actual timing and content of the completed BLA filing for
Aldurazyme; the content and timing of decisions made by the FDA and the EMEA
regarding Aldurazyme; the ability to manufacture sufficient quantities of
product for development and commercialization activities and to do so in a
timely manner; enrollment rates for clinical trials; the continued funding of
the joint venture between Genzyme and BioMarin; decisions made by physicians and
third party payers regarding the use of and reimbursement for Aldurazyme; our
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 our ability to
commercialize Aldurazyme; the competitive environment for therapies for MPS I;
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 2001 Annual Report on Form 10-K. 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 the those reports.
Genyzme 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 of Genzyme Corporation. AldurazymeTM is a
trademark of BioMarin/Genzyme LLC.
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BioMarin's press releases and other company information are available online at
http://www.biomarinpharm.com.
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