BioMarin to Advance BMN-701 for Pompe Disease to Next Phase of Development

BioMarin to Advance BMN-701 for Pompe Disease to Next Phase of Development

             BMN-701 Meaningfully Improves Respiratory Endpoints
          Phase 2/3 Switch Study Expected to Begin by December 2013

         Conference Call and Webcast to Be Held Today at 5:00 p.m. ET

SAN RAFAEL, Calif., March 19, 2013 (GLOBE NEWSWIRE) -- BioMarin Pharmaceutical
Inc. (Nasdaq:BMRN) announced today results from POM-001, the Phase 1/2 trial
for BMN-701, a fusion protein of insulin-like growth factor 2 and acid
alpha-glucosidase (IGF2-GAA) for the treatment of late-onset Pompe disease.
The results exceeded the company's pre-specified requirements for proceeding
to the next phase of development by showing that in the 20 mg/kg every other
week dose cohort, three out of 16 patients, or 19 percent, had a greater than
75 meter improvement in 6-minute walk distance, and that there was a 14.1
percent relative improvement in Maximal Expiratory Pressure (MEP) and a 27.0
percent relative improvement in Maximal Inspiratory Pressure (MIP) from
pre-treatment baseline to week 24, two important measures of overall
respiratory muscle function and strength. Pending a review with regulatory
authorities, the company expects to continue development of BMN-701 by
initiating a Phase 2/3 switching trial by the end of 2013 in late-onset Pompe
patients who have previously been treated with alglucosidase alfa

"More than half of late-onset Pompe patients require ventilatory assistance,
and many more patients have impairments directly related to weakness of
breathing muscles. This means that a therapy that improves respiratory muscle
function substantially would be important and welcome and could help delay
premature death in Pompe disease," said Professor Benedikt Schoser of the
Friederich-Baur Institute and speaker of the German working group for Pompe

"The findings from this study point the way forward for a potentially
meaningful advance in the management of late-onset Pompe patients. Pompe is a
disease that destroys muscle tissue throughout the body, including the muscles
of respiration.Maximal Expiratory Pressure (MEP) and Maximal Inspiratory
Pressure (MIP) are direct measures of respiratory muscle function and likely
an important indicator of a drug's effectiveness in this setting.The
improvements in MEP and MIP that BMN-701 patients demonstrated is a unique and
important finding," said Barry Byrne, M.D., Ph.D., Professor, Pediatrics and
Molecular Genetics & Microbiology and Director, University of Florida Powell
Center, and lead investigator for POM-001."If treatment with BMN-701 results
in improvements in these important respiratory functional measures in patients
who have already experienced a maximal benefit from current therapy, BMN-701
could become an important treatment option," Byrne said.

Phase 1/2 Study: Efficacy and Safety

The mean improvement in 6-minute walk distance was approximately 22 meters for
the 16 patients treated in the 20 mg/kg cohort.In addition, there were three
super-responders, or 19 percent of patients, who experienced greater than a 75
meter improvement in 6-minute walk distance from baseline to week 24.For
pulmonary function, mean improvement in percent predicted forced vital
capacity (FVC) was 1.2 percent in absolute terms, or a 2.0 percent relative
improvement from pre-treatment baseline to week 24.Mean improvement
inmaximum voluntary ventilation (MVV) was 2.9 L/min in absolute terms, or a
4.3 percent relative improvement from pre-treatment baseline to week 24. Mean
improvement in percent predicted maximal expiratory pressure (MEP) was 5.1
percent in absolute terms, or a 14.1 percent relative improvement from
pre-treatment baseline to week 24.Mean improvement in percent predicted
maximal inspiratory pressure (MIP) was 11.0 percent in absolute terms, or a
27.0 percent relative improvement from pre-treatment baseline to week 24.The
company conducted a responder analysis in which each patient was assigned a
score of plus one for improvement of more than 10 percent and minus one for a
decline of 10 percent in the domains of 6-minute walk test, MEP and MIP.Each
patient's scores were aggregated by summing the individual domain scores for
that patient.Thirteen of the 16 patients scored a plus one or greater; two
patients had a score of 0, consistent with stabilization, and one patient
declined in one domain.

Side effects for BMN-701 were generally consistent with those seen for other
enzyme replacement therapies.The principal clinical adverse event was
infusion-associated reaction in two patients, resulting in temporary drug
interruption in one patient and drug withdrawal in one
patient.Infusion-associated hypoglycemia, an expected pharmacologic effect of
BMN-701, occurred in 13 patients in the 20 mg/kg cohort.All hypoglycemia
events occurred during or within one hour of infusion,were transient and
readily manageable through diet and predominantly asymptomatic.

Table: BMN-701 Phase 1/2 Results as Compared to LOTS Study*

                  POM-001                             LOTS          
                  BMN-701                             Alglucosidase 
          Baseline Change from baseline % Chg  Baseline Change from   % Chg
                  at Week 24                          at Week 26    
Avg. 6MWT 354.5    22.3                  6.3%   332.2    28.5          8.6%
Super     n= 16    3                     18.8%  n=60     4             6.7%

                 POM-001                   LOTS
                 BMN-701                   Alglucosidase Alfa
         Baseline Week 24 Change    % Chg    Baseline Week  Change    % Chg
                        %        from                   %        from
                           predicted baseline                  predicted baseline
FVC      58.1%    59.3%   1.2%      2.0%      55.4%    56.9% 1.5%      2.7%
MVV      67.6     70.6    2.9       4.3       na       na    na        na
MEP      36.4%    41.6%   5.1%      14.1%     32.0%    34.6% 2.6%      8.0%
MIP      40.6%    51.6%   11.0%     27.0%     40.0%    45.0% 5.0%      12.5%

*The LOTS trial (N Engl J Med 2010;362:1396-406) was a randomized,
placebo-controlled trial of alglucosidase alfa, recombinant human GAA, for the
treatment of late-onset Pompe's disease.Ninety patients who were eight years
ofage or older, ambulatory, and free of invasive ventilation were randomly
assigned to receive biweekly intravenousalglucosidase alfa (20 mg/kg) or
placebo.The two primary endpoints were 6-minute walk distance and
percentageof predicted forced vital capacity (FVC). Comparison to LOTS study
data roughly estimated at week 26 are presented toprovide additional
information regarding BioMarin's decision making process for the continued
development ofBMN-701.As the trials were independently conducted and
utilized different protocols, no inference should be made about the
comparative efficacy of the products tested.

"We are excited by the findings of our first study of BMN-701 in previously
untreated Pompe patients.We observed meaningful improvements in mean 6-minute
walk distance and very substantial walk improvements for some patients, plus
significant improvements in respiratory muscle strength.Importantly, there
were improvements in one or more walk or respiratory domains in nearly all
patients.Based on discussions with Pompe KOLs who have reviewed this data, we
believe there will be broad interest to participate in our planned Phase 2/3
study," said Hank Fuchs, M.D., Chief Medical Officer of BioMarin.

Next Phase of Development: Phase 2/3 Study

The company expects to initiate a Phase 2/3 switching trial by the end of 2013
in late-onset Pompe patients who have previously been treated with
alglucosidase alfa.Subject to discussions with health authorities, the
proposed study design is a single arm trial, with treatment at 20 mg/kg
administered every other week for 24 weeks.The company intends to use
efficacy as measured by the respiratory parameter MIP as the primary
endpoint.Secondary objectives include MEP and six-minute walk test, as well
as safety.The study will be conducted with full scale material from a revised
manufacturing process, which has improved process robustness and increased

POM-001 Phase 1/2 Study Design

The Phase 1/2 trial is an open-label study to evaluate the safety,
tolerability, pharmacokinetics, pharmacodynamic and clinical activity of
BMN-701 administered as an intravenous infusion every two weeks at doses of 5
mg/kg, 10 mg/kg and 20 mg/kg.The company enrolled 22 patients between the
ages of 18 and 65 years old with late-onset Pompe disease for a treatment
period of 24 weeks.

Conference Call Details

BioMarin will host a conference call and webcast today, Tuesday, March 19,
2013 at 5:00 p.m. ET. This event can be accessed on the investor section of
the BioMarin website at

Date: March 19, 2013
Time: 5:00 p.m. ET

U.S. / Canada Dial-in Number: (877) 303-6313
International Dial-in Number:(631) 813-4734
Conference ID: 24529793

Replay Dial-in Number: (855) 859-2056
Replay International Dial-in Number: (404) 537-3406
Conference ID: 24529793

About Pompe Disease

Pompe Disease is an autosomal recessive metabolic disorder which damages
muscle and nerve cells throughout the body.It is caused by an accumulation of
glycogen in the lysosome due to deficiency of the lysosomal acid
alpha-glucosidase enzyme.The build-up of glycogen causes progressive muscle
weakness (myopathy) throughout the body and affects various body tissues,
particularly in the heart, skeletal muscles, liver and nervous
system.Measurement of maximal inspiratory and expiratory pressures are used
to assess pulmonary muscle function. Maximal inspiratory pressure (MIP) is the
maximal pressure that can be produced by the patient trying to inhale through
a blocked mouthpiece. Maximal expiratory pressure (MEP) is the maximal
pressure measured during forced expiration through a blocked mouthpiece after
a full inhalation.Current treatment options for Pompe disease include
Lumizyme and Myozyme.On April 28, 2006 the US Food and Drug Administration
approved a Biologic License Application (BLA) for Myozyme (alglucosidase alfa,
rhGAA),the first treatment for patients with Pompe disease. On May 26, 2010
FDA approved Lumizyme, a similar version of Myozyme, for the treatment of
late-onset Pompe disease.Lumizyme and Myozyme have the same generic
ingredient (Alglucosidase Alfa). Myozyme is made using a 160-L bioreactor,
while the Lumizyme uses a 4000-L bioreactor.

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 BMN-110
(N-acetylgalactosamine 6-sulfatase), formally referred to as GALNS, which
successfully completed Phase III clinical development for the treatment of MPS
IVA, 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-natriuretic peptide, which is currently in Phase I clinical development for
the treatment of achondroplasia. For additional information, please visit Information on BioMarin's website is not incorporated by
reference into this press release.

The BioMarin Pharmaceutical Inc. logo is available at

Forward-Looking Statement

This press release contains forward-looking statements about the business
prospects of BioMarin Pharmaceutical Inc., including, without limitation,
statements about: the development of BioMarin's BMN-701 program generally, the
timing and design of the planed Phase 3 trial of BMN-701, and expectations
regarding the final results of the Phase 2 trial following final statistical
analysis. 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:differences
in the final analysis of the data from the BMN-701 Phase 1/2 trial, results
and timing of current and planned preclinical studies and clinical trials of
BMN-701; the content and timing of decisions by the U.S. Food and Drug
Administration, the European Commission and other regulatory authorities;
BioMarin's ability to secure clinical trial sites to perform the Phase 3 trial
and the ability to enroll patients into those trials; the ability to timely
manufacture suitable clinical trial material using the revised manufacturing
process 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 Annual Report on Form 10-K for
the Year ended December 31, 2012. 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:
         Eugenia Shen
         BioMarin Pharmaceutical Inc.
         (415) 506-6570
         Debra Charlesworth
         BioMarin Pharmaceutical Inc
         (415) 455-7451

BioMarin Pharmaceutical Inc. Logo
Press spacebar to pause and continue. Press esc to stop.