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BioMarin Phase 3 Study of GALNS for the Treatment of MPS IVA Meets Primary Endpoint



BioMarin Phase 3 Study of GALNS for the Treatment of MPS IVA Meets Primary
Endpoint

      Company Plans to Submit Marketing Applications Starting in 1Q 2013

         Conference Call and Webcast to be Held Today at 8:30 a.m. ET

SAN RAFAEL, Calif., Nov. 5, 2012 (GLOBE NEWSWIRE) -- BioMarin Pharmaceutical
Inc. (Nasdaq:BMRN) announced today that the pivotal Phase 3 study of GALNS met
the primary endpoint of change in six-minute walk distance compared with
placebo at 24 weeks in subjects receiving weekly infusions of GALNS at the
dose of 2 mg/kg (p=0.0174). MOR-004 was a randomized, double-blind,
placebo-controlled study evaluating two doses of GALNS (BMN-110, N-
acetylgalactosamine-6-sulfatase) for the treatment of patients with the rare
lysosomal storage disorder Mucopolysaccharidosis Type IVA (MPS IVA), also
called Morquio A Syndrome. Patients dosed with GALNS at 2 mg/kg every other
week did not show a meaningful or statistically significant change from
baseline compared to placebo. The company also announced preliminary data from
the MOR-005 extension study which suggests that clinical benefits continue to
improve with further dosing with GALNS. Only a limited number of patients have
reached the 36 or 48 week points of total time on treatment in the extension
study, and the results will be updated when the study is completed. The
company confirmed that based on the results of MOR-004, and following planned
discussions with regulatory authorities, it expects to submit marketing
applications starting in the first quarter of 2013.

Treatment with GALNS Significantly Improves Primary Endpoint

The primary endpoint of the study, change in six-minute walk distance at 24
weeks, was statistically significant in patients dosed with GALNS at 2 mg/kg
every week with a mean increase of 22.5 meters (p=0.0174) over placebo. In
MOR-004, patients dosed at 2 mg/kg every week showed an improvement in
six-minute walk distance at week 12 compared to baseline and showed continued
improvement at week 24. Preliminary analysis of a subset of the patients in
the MOR-005 extension study who have reached the 36 week and 48 week
timepoints in the study also showed further improvement at weeks 36 and 48.

Treatment with GALNS Improves Both Secondary Endpoints

On the secondary endpoint of three-minute stair climb, patients dosed with
GALNS at 2 mg/kg every week showed a trend toward improvement at 24 weeks of
1.1 additional stairs per minute over placebo. In MOR-004, patients dosed with
GALNS at 2 mg/kg every week showed an improvement in three-minute stair climb
performance at week 12 compared to baseline and showed continued improvement
at week 24. Preliminary analysis of a subset of patients in the extension
study (MOR-005) who have reached the 36 week and 48 week timepoints in the
study also showed further improvement in three-minute stair climb performance.

In the other secondary endpoint, urinary keratan sulfate (KS) levels, patients
dosed with GALNS at 2 mg/kg every week showed consistent and robust reduction
in urinary KS with a mean difference from baseline as compared to placebo of
40.7 percent (p less than 0.0001). Preliminary analysis of a subset of
patients in the extension study (MOR-005) who have reached the 36 week and 48
week timepoints in the study showed this level of reduction was maintained.

Treatment with GALNS Improves Pulmonary Function

Pulmonary function, as defined by maximum voluntary ventilation (MVV) was
measured at 24 weeks. In MOR-004, patients dosed with GALNS at 2 mg/kg every
week showed a trend toward improvement from baseline of 10.3 percent over
placebo. Preliminary analysis of the subset of patients who reached the 48
week timepoint showed a reduction in the improvement, though an increase over
baseline was maintained.

Pulmonary function, as defined by forced vital capacity (FVC) was measured at
24 weeks. In MOR-004, patients dosed with GALNS at 2 mg/kg every week showed a
trend toward improvement from baseline of 3.3 percent over
placebo. Preliminary analysis of the subset of patients who reached the 48
week timepoint showed continued improvement.

Safety Summary

In MOR-004, GALNS was generally well-tolerated and adverse events were similar
to those seen in clinical trials of other enzyme replacement therapies. The
most common adverse events occurring in more than 25 percent of treated
patients included vomiting, pyrexia, headache, nausea and cough. Serious
adverse events that were thought to be related to study drug occurred in 3.4
percent of the weekly group, 1.7 percent of the every other week group and 0
percent in the placebo group. There were no deaths and no patients withdrew
from the study due to an adverse event.

Infusion-associated reactions were generally mild to moderate and manageable
with symptomatic treatment and/or infusion rate modification. Of the 1,345
total number of infusions in the weekly dose group, 17 infusions (1.3 percent)
were interrupted or discontinued due to an adverse event. All patients
subsequently resumed dosing.

"The positive results from this pivotal study will help support GALNS as the
first therapy available to help the approximate 3,000 people worldwide
suffering from MPS IVA -- a rare, degenerative, life-threatening genetic
condition with no available therapy," said Hank Fuchs, M.D., Chief Medical
Officer at BioMarin. "We are very pleased with the clarity that the MOR-004
study has provided us with respect to the appropriate dosing of GALNS. The
weekly 2 mg/kg dose provided a statistically significant and clinically
meaningful improvement in the study's primary endpoint, and positive trends
toward improvement in other clinically meaningful endpoints, including
three-minute stair climb and pulmonary function tests. By contrast, the 2
mg/kg every other week dose was shown to be similar to placebo on the primary
and clinical secondary and tertiary endpoints. We look forward to reviewing
the results of this study with regulatory authorities, and applying for
marketing authorizations starting in the first quarter of 2013."

"The GALNS clinical program is currently the highest development priority at
BioMarin, and this positive Phase 3 study serves as a potentially
transformative milestone for the company," said Jean-Jacques Bienaimé, CEO of
BioMarin. "We are applying our track record of success in developing novel
treatments for orphan diseases and our existing commercial infrastructure for
Naglazyme to bring GALNS to patients as rapidly as we can."

Top-line Results: Primary, and Secondary and Tertiary Endpoints

6 Minute Walk Distance                                      
                       Change from Baseline in Meters      Change vs Placebo
                       (Observed data)                     (Modeled treatment
                                                           effect)
                                                            
                       Placebo  2.0 mg/kg/every 2.0 mg/kg/ 2.0 mg/kg/weekly
                               other week       weekly
                                                            
MOR-004                                                     
Week 12                                                     
Mean                   12.7    13.5             23.7        
n                      59      59               58          
                                                            
Week 24                                                     
Mean                   13.5    14.9             36.5       22.5
n                      59      58               57         p=0.0174^*
                                                            
MOR-005 (Interim data)                                      
                                                            
Week 36                                                     
Mean                    N/A    17.0             46.6        
n                       N/A    27               27          
                                                            
Week 48                                                     
Mean                    N/A    3.8              45.4        
n                       N/A    18               13          
                                                            
                                                            
3 Minute Stair Climb                                        
                       Change from Baseline in Stairs per  Change vs Placebo
                       Minute
                       (Observed data)                     (Modeled treatment
                                                           effect)
                                                            
                       Placebo 2.0 mg/kg/every  2.0 mg/kg/ 2.0 mg/kg/weekly
                               other week       weekly
                                                            
MOR-004                                                     
Week 12                                                     
Mean                   2.9     3.6              3.6         
n                      59      59               58          
                                                            
Week 24                                                     
Mean                   3.6     3.4              4.8        1.1
n                      59      58               57         p=0.4935*
                                                            
MOR-005 (Interim data)                                      
Week 36                                                     
Mean                    N/A    5.3              6.5         
n                       N/A    27               27          
                                                            
Week 48                                                     
Mean                    N/A    5.8              7.1         
n                       N/A    18               16          
                                                            
                                                            
Urinary Keratan Sulfate                                     
                       Percentage Change from Baseline     % Change vs Placebo
                       (ug/mg)
                       (Observed data)                     (Modeled treatment
                                                           effect)
                                                            
                       Placebo 2.0 mg/kg/every  2.0 mg/kg/ 2.0 mg/kg/ weekly
                               other week       weekly
                                                            
MOR-004                                                     
Week 12                                                     
Mean                   (1.6)   (20.9)           (41.8)      
n                      56      58               55          
                                                            
Week 24                                                     
Mean                   (4.4)   (35.2)           (45.1)     (40.7)
n                      55      57               54         p less than 0.0001*
                                                            
MOR-005 (Interim data)                                      
                                                            
Week 36                                                     
Mean                    N/A    (30.2)           (45.8)      
n                       N/A    25               19          
                                                            
Week 48                                                     
Mean                    N/A    (31.7)           (45.9)      
n                       N/A    9                10          
                                                            
                                                            
Pulmonary Function                                          
                       Percentage Change from Baseline     % Change vs Placebo
                       (Observed data)                     (Modeled treatment
                                                           effect)
                                                            
                       Placebo 2.0 mg/kg/every  2.0 mg/kg/ 2.0 mg/kg/ weekly
                               other week       weekly
Maximum Voluntary                                           
Ventilation (MVV)
MOR-004                                                     
Week 24                                                     
Mean                   2.4     6.1              10.8       10.3
n                      50      52               49         p=0.0943*
                                                            
MOR-005 (Interim data)                                      
Week 48                                                     
Mean                   N/A     15.5             1.1         
n                      N/A     16               9           
Forced Vital Capacity                                       
(FVC)
MOR-004                                                     
Week 24                                                     
Mean                   1.5     4.1              4.9        3.3
n                      53      55               55         p=0.3041*
                                                            
MOR-005 (Interim data)                                      
Week 48                                                     
Mean                    N/A    6.3              6.1         
n                       N/A    16               12          

* P-values are based on the pre-specified primary statistical analysis
model. Mean changes vs placebo are the treatment effects based on this model
and may differ slightly from the means of the observed data.

Study Design

The MOR-004 Phase 3 study was a randomized, double-blind placebo-controlled
clinical study to evaluate the efficacy and safety of 2.0 mg/kg/week and 2.0
mg/kg/every other week of GALNS in patients with MPS IVA. The primary endpoint
was the change in six-minute walk distance from baseline to week 24 compared
to placebo, and the secondary endpoints were the changes in three-minute stair
climb test and urine KS levels compared to placebo.

MOR-005 is the extension study for the pivotal Phase 3 study for GALNS
(MOR-004). Patients from the two treatment arms of 2 mg/kg/week and 2
mg/kg/every other week remained on the same dose, and the placebo patients
were randomized into one of the treatment groups. Preliminary data presented
in this press release includes only patients from the two active treatment
arms of MOR-004 who have reached 36 and 48 weeks of total treatment time as of
September 14, 2012.

To be eligible for the study, subjects had to be at least five years of age,
have a documented clinical diagnosis of MPS IVA and have an average screening
six-minute walk test distance ≥30 meters and ≤325 meters.

This is the largest Phase 3 enzyme replacement therapy (ERT) study to date
with 176 patients treated at 31 sites in 17 countries. 

The baseline measurements, including age, six-minute walk distance,
three-minute stair climb and urinary KS were well-balanced across the three
arms of the study.

Results presented are preliminary and subject to final analysis. Complete
results will be presented at the WORLD Symposium in mid-February 2013.

Conference Call Details

BioMarin will host a conference call and webcast to discuss results for the
GALNS Phase 3 trial today, Monday, November 5, at 8:30 a.m. ET. This event can
be accessed on the investor section of the BioMarin website at www.BMRN.com.

Date: November 5, 2012
Time: 8:30 a.m. ET 
U.S. / Canada Dial-in Number: 877.303.6313
International Dial-in Number: 631.813.4734
Conference ID: 64771689
 
Replay Dial-in Number: 855.859.2056 
Replay International Dial-in Number: 404.537.3406 
Conference ID: 64771689

About MPS IVA

Mucopolysaccharidosis IVA (MPS IVA, also known as Morquio A Syndrome) is a
disease characterized by deficient activity of
N-acetylgalactosamine-6-sulfatase (GALNS) causing excessive lysosomal storage
of keratan sulfate (KS). This excessive storage causes a systemic skeletal
dysplasia, short stature, and joint abnormalities, which limit mobility and
endurance. Malformation of the thorax impairs respiratory function, and
odontoid hypoplasia and ligamentous laxity cause cervical spinal instability
and potentially cord compression. Other symptoms may include hearing loss,
corneal clouding, and heart valvular disease. Initial symptoms often become
evident in the first five years of life. Depending on severity of the disease,
age of diagnosis will vary.

The rate of incidence of MPS IVA is as yet unconfirmed and varies among
different populations but estimates vary between 1 in 200,000 live births and
1 in 250,000 live births. The estimated prevalence is between 1,000 and 1,500
patients in the U.S., EU and Japan and between 1,500 to 2,000 patients in the
rest of the world for a total of 2,500 to 3,000 patients.

About BioMarin

BioMarin develops and commercializes innovative biopharmaceuticals for serious
diseases and medical conditions. The company's product portfolio comprises
four approved products and multiple clinical and pre-clinical product
candidates. Approved products include Naglazyme® (galsulfase) for
mucopolysaccharidosis VI (MPS VI), a product wholly developed and
commercialized by BioMarin; Aldurazyme® (laronidase) for mucopolysaccharidosis
I (MPS I), a product which BioMarin developed through a 50/50 joint venture
with Genzyme Corporation; Kuvan® (sapropterin dihydrochloride) Tablets, for
phenylketonuria (PKU), developed in partnership with Merck Serono, a division
of Merck KGaA of Darmstadt, Germany; and Firdapse™ (amifampridine), which has
been approved by the European Commission for the treatment of Lambert Eaton
Myasthenic Syndrome (LEMS). Product candidates include GALNS
(N-acetylgalactosamine 6-sulfatase), which is currently in Phase III clinical
development for the treatment of MPS IVA, amifampridine phosphate
(3,4-diaminopyridine phosphate), which is currently in Phase III clinical
development for the treatment of LEMS in the U.S., PEG-PAL (PEGylated
recombinant phenylalanine ammonia lyase), which is currently in Phase II
clinical development for the treatment of PKU, BMN-701, a novel fusion protein
of insulin-like growth factor 2 and acid alpha glucosidase (IGF2-GAA), which
is currently in Phase I/II clinical development for the treatment of Pompe
disease, BMN-673, a poly ADP-ribose polymerase (PARP) inhibitor, which is
currently in Phase I/II clinical development for the treatment of
genetically-defined cancers, and BMN-111, a modified C-nutriuretic peptide,
which is currently in Phase I clinical development for the treatment of
achondroplasia. For additional information, please visit www.BMRN.com.
Information on BioMarin's website is not incorporated by reference into this
press release.

The BioMarin Pharmaceutical Inc. logo is available at
http://www.globenewswire.com/newsroom/prs/?pkgid=11419

Forward-Looking Statement

This press release contains forward-looking statements about the business
prospects of BioMarin Pharmaceutical Inc., including, without limitation,
statements about: the expectations related to the continued clinical
development of its product candidate GALNS; expectations regarding the final
analysis of the GALNS Phase 3 clinical trial data; expectations for the
results of the extension trial of GALNS; 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 and planned preclinical studies and clinical trials of
GALNS; the final analysis of the results of the Phase 3 trial of GALNS; our
ability to successfully manufacture our products and product candidates; the
content and timing of decisions by the U.S. Food and Drug Administration, the
European Commission and other regulatory authorities concerning GALNS 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 2011 Annual Report on Form 10-K, and the
factors contained in BioMarin's reports on Form 10-Q. 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®, Naglazyme®, Kuvan® and Firdapse™ are registered trademarks of
BioMarin Pharmaceutical Inc.

Aldurazyme® is a registered trademark of BioMarin/Genzyme LLC.

CONTACT: Investors and Media
         Eugenia Shen
         BioMarin Pharmaceutical Inc.
         (415) 506-6570

BioMarin Pharmaceutical Inc. Logo
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