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BIOMARIN RE-ACQUIRES RIGHTS TO KUVAN IN CANADA FROM MERCK
SERONO |
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In December BioMarin re-acquired rights to Kuvan in Canada, which will
enable the company to better coordinate commercialization efforts in the
North American market. Terms of the agreement specify a reduction in royalties
owed to BioMarin on Merck Serono sales outside the United States and Japan. |
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KUVAN APPROVED BY FDA; LAUNCHED IMMEDIATELY IN THE U.S. |
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Approximately three years after filing the IND, BioMarin received FDA
approval for KuvanTM (sapropterin dihydrochloride) Tablets, the first specific
drug therapy for the treatment of phenylketonuria (PKU). The product was
launched in the U.S. immediately following the FDA approval. Kuvan is indicated
to reduce blood phenylalanine (Phe) levels in patients with hyperphenylalaninemia
(HPA) due to tetrahydrobiopterin (BH4) responsive PKU and is to be used
in conjunction with a Phe-restricted diet. |
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BIOMARIN AND IGAN COLLABORATE ON DEVELOPMENT OF ENZYME
THERAPY TO TREAT IGA NEPHROPATHY |
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BioMarin and IGAN Biosciences initiated a program to develop an IgA protease
for treating IgA nephropathy, an orphan designated kidney disorder with
few treatment alternatives. In the United States, approximately 800 patients
per year develop end stage renal disease caused by IgA nephropathy. An estimated
40,000 are affected by the disorder. |
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BIOMARIN FILES IND FOR PEG-PAL FOR THE TREATMENT OF PKU |
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In November, BioMarin filed an investigational new drug application (IND)
with the FDA for PEG-PAL (PEGylated recombinant phenylalanine ammonia lyase),
formerly known as PhenylaseTM, for the treatment of phenylketonuria (PKU).
The company expects to initiate a clinical study of PEG-PAL in PKU patients
in the first quarter of 2008. Preclinical data has demonstrated that PEG-PAL
administered subcutaneously once weekly to PKU mice resulted in a sustained
decrease in blood phenylalanine (Phe) levels in a twelve week study and
has also shown potent Phe level reductions in primates. |
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MAA FOR SAPROPTERIN FOR HYPERPHENYLALANINEMIA SUBMITTED
TO EMEA |
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November-BioMarin partner Merck Serono, a division of Merck KGaA, Darmstadt,
Germany, submitted a Marketing Authorization Application (MAA) to the European
Medicines Agency (EMEA) for sapropterin dihydrochloride (known as KuvanTM
in the U.S.) an oral treatment for patients suffering from significant hyperphenylalaninemia
(HPA) due to phenylketonuria (PKU) or tetrahydrobiopterin (BH4) deficiency.
Acceptance of the MAA filing by the EMEA will trigger a $15 million milestone
payment to BioMarin. Sapropterin has received orphan medicinal product designation
in the European Union. |
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EXCLUSIVE RIGHTS TO KUVAN DATA LICENSED TO ASUBIO PHARMA |
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September-BioMarin has licensed exclusive rights to data and intellectual
property contained in the Kuvan (sapropterin dihydrochloride) NDA to long-standing
partner, Asubio Pharma Co., Ltd. (a subsidiary of Daiichi Sankyo). Asubio
will use this data to supplement its current filing to the Japanese Ministry
of Health, Labour and Welfare for approval of its BH4 product for the treatment
of PKU in Japan. This new data greatly expands the clinical data set on
treatment of PKU and is expected to accelerate the timing for the label
extension of Asubio's current BH4 product. BioMarin will receive a milestone
payment for approval as well as double-digit royalties on net sales of BH4
for PKU in Japan. |
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BIOMARIN LICENSES CYSTIC FIBROSIS TECHNOLOGY FROM UCSF |
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August-BioMarin has licensed from the University of California, San Francisco,
intellectual property covering compounds demonstrated to improve cystic
fibrosis transmembrane conductance regulator (CFTR) protein functionality.
Lead compounds are expected to undergo additional animal testing and optimization,
with the goal of filing an IND in 2009. Cystic fibrosis is a well-defined
and relatively widespread orphan disease affecting an estimated 30,000 patients
in the U.S./40,000 patients outside the U.S. |
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BLA FOR NAGLAZYME SUBMITTED TO JAPANESE MINISTRY OF HEALTH |
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AnGes MG, Inc. (AnGes), BioMarin's marketing and distribution partner
in Japan submitted a Biologics License Application (BLA) for Naglazyme®
(galsulfase) to the Japanese Ministry of Health, Labour and Welfare. If
approved, Naglazyme will be the first drug treatment option to MPS VI patients
in Japan. Naglazyme has obtained an orphan designation in Japan. |
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KUVAN RECEIVES PRIORITY REVIEW STATUS FROM FDA |
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July-Priority review status is an FDA designation granted to drugs that,
if approved, will provide a significant improvement in the safety or effectiveness
of the treatment, diagnosis, or prevention of a serious or life-threatening
disease. |
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BIOMARIN INITIATES EXPANDED ACCESS PROGRAM FOR KUVAN IN
THE U.S. |
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In June, the first patient initiated treatment in BioMarin's expanded
access program for Kuvan. Under an expanded access program, the FDA allows
early access to investigational drugs being developed to treat serious diseases
for which there is no satisfactory alternative therapy. BioMarin will provide
Kuvan at no charge to up to 500 U.S. patients throughout the duration of
the program. |
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BIOMARIN SUBMITS NDA FOR KUVAN FOR PKU |
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May-The NDA filing contains data evaluating Kuvan in approximately 650
human subjects in six clinical studies and represents BioMarin's largest
and most comprehensive filing to date. The fully electronic NDA filing includes
a comprehensive set of preclinical, clinical and manufacturing related data
on Kuvan. If the FDA accepts the NDA and grants the request for priority
review, the FDA is expected to take action on the application within six
months of its submission. Kuvan has received the orphan drug designation,
which allows for seven years of market exclusivity within the United States
following FDA approval. |
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BIOMARIN INITIATES PHASE 2A CLINICAL STUDY OF 6R-BH4 IN
SICKLE CELL DISEASE |
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In May, the first patient initiated treatment in the Phase 2a clinical
study of 6R-BH4 (sapropterin dihydrochloride) for the treatment of sickle
cell disease (SCD). The company expects to announce data from this study
in the first half of 2008. SCD is an orphan disease with 70,000 to 100,000
patients in the U.S. It is well- diagnosed at birth, but there is only one
approved drug treatment option currently available which is used by a minority
of patients due to toxicity problems. The Phase 2a multi-center, open-label
study will evaluate the safety of oral 6R- BH4 administered in escalating
doses in patients with sickle cell disease, as well as changes in physiological
and biochemical markers of endothelial function which underlie some key
aspects of SCD. |
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RESULTS FROM PHASE 2 CLINICAL STUDY OF 6R-BH4 IN POORLY
CONTROLLED HYPERTENSION |
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February-Results demonstrated that there was no statistically significant
or clinically meaningful effect of 6R-BH4 on any efficacy or safety parameter
measured, relative to placebo, despite encouraging pre-clinical and clinical
studies of 6R-BH4 in diseases with endothelial dysfunction. BioMarin will
analyze this data in detail to better understand the results. |
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POSITIVE RESULTS FROM PHASE 3 DIET STUDY OF PHENOPTIN
FOR PKU |
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January-All pre-specified efficacy and safety endpoints of the double-blind,
placebo-controlled Phase 3 diet study of Phenoptin(TM) (sapropterin dihydrochloride)
were met. Treatment resulted in a significant increase in patients' phenylalanine
tolerance as well as a reduction in their blood phenylalanine levels. In
addition, the data showed that Phenoptin was well tolerated in younger PKU
patients under dietary control. |
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PHASE 2 CLINICAL STUDY OF 6R-BH4 IN PERIPHERAL ARTERIAL
DISEASE INITIATED |
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In January, the first patient initiated treatment in the Phase 2 clinical
study of 6R-BH4 for the treatment of symptomatic peripheral arterial disease.
The company expects to announce data from this study in the first half of
fiscal year 2008. Peripheral arterial disease results from endothelial dysfunction
and affects approximately eight million Americans, many of whom also suffer
from intermittent claudication. The Phase 2, multicenter, multinational,
randomized, double-blind, placebo-controlled study is designed to compare
oral 6R-BH4 to placebo in subjects with intermittent claudication (IC) caused
by peripheral arterial disease. |
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POSITIVE RESULTS FROM PHASE 3 EXTENSION STUDY OF PHENOPTIN
FOR PKU |
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December-Data has confirmed the long-term safety, tolerability and efficacy
of Phenoptin to control blood Phe levels across a range of doses in PKU
patients. The company is on track to file the NDA in the second quarter
of 2007. A once daily dose regimen of Phenoptin was sufficient to maintain
the reduction of blood Phe levels throughout a 24 hour period. The incidence
and type of adverse events were comparable to that of the placebo group
during the double-blind study and nearly all were mild or moderate in severity. |
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ALDURAZYME RECEIVES MARKETING APPROVAL IN JAPAN |
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October-Japan's Ministry of Health, Labor, and Welfare (MHLW) has granted
marketing authorization for Aldurazyme® (laronidase), the first specific
treatment for MPS I approved in Japan. Aldurazyme has been designated as
an orphan drug in Japan. |
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ORAPRED ODT LAUNCHED BY ALLIANT PHARMACEUTICALS |
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August-Orapred ODT™ (prednisolone sodium phosphate orally disintegrating
tablets), the first FDA-approved orally disintegrating tablet form of prednisolone,
is now available in the United States. The Orapred product line, which includes
Orapred ODT and Orapred® (prednisolone sodium phosphate oral solution)
is marketed by Alliant Pharmaceuticals, Inc. Under the terms of the marketing
agreement, BioMarin will receive milestone payments and royalties on Orapred
products sales. BioMarin will retain commercial rights to the Orapred product
line outside of North America. |
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PHASE 2 CLINICAL STUDY OF 6R-BH4 IN POORLY CONTROLLED
HYPERTENSION INITIATED |
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In July, the first patient initiated treatment in the Phase 2 clinical
study of 6R-BH4 for the treatment of poorly controlled hypertension. The
company hopes to announce data from this study in early 2007 that will confirm
results seen earlier in pilot clinical studies that demonstrated that oral
administration of 6R-BH4 can reduce blood pressure in individuals who remain
hypertensive despite treatment with other medications. |
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BIOMARIN AND ALLIANT PHARMACEUTICALS ESTABLISH NORTH AMERICAN
LICENSING AGREEMENT FOR ORAPRED |
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March-The licensing and acquisition agreement provides exclusive North
American rights to Alliant for the Orapred® (prednisolone sodium phosphate
oral solution) product line, including Orapred ODT™ (prednisolone sodium
phosphate orally disintegrating tablets). BioMarin will receive payments
and royalties based on the product's approval, launch and level of sales.
BioMarin will retain commercial rights outside of North America. |
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POSITIVE RESULTS FROM PHASE 3 CLINICAL STUDY OF PHENOPTIN
FOR PKU |
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In March, positive results of a Phase 3, double-blind, placebo-controlled
clinical study of Phenoptin™ (sapropterin dihydrochloride) confirmed
that all pre-specified primary and secondary endpoints were met. Data demonstrates
a statistically significant reduction at six weeks in blood phenylalanine
(Phe) levels (p<0.0001) in patients receiving Phenoptin, compared with
those receiving placebo. |
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NAGLAZYME RECEIVES EUROPEAN UNION APPROVAL |
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January-The European Commission has granted marketing authorization for
Naglazyme™ (galsulfase), the first treatment for MPS VI approved in
the European Union. Naglazyme has been granted orphan drug status in the
EU, which confers 10 years of market exclusivity. BioMarin will launch the
product on a country-by-country basis. |
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PHENOPTIN FOR PKU RECEIVES FDA FAST TRACK DESIGNATION |
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In January, the U.S. Food and Drug Administration (FDA) granted Fast Track
designation for Phenoptin™ (sapropterin dihydrochloride) for PKU, currently
in Phase 3 clinical development.
The Fast Track program is designed to expedite the development and review
process of new drugs that are intended to treat serious or life-threatening
conditions and that demonstrate the potential to address unmet medical needs. |
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BIOMARIN ESTABLISHES COMMERCIAL OPERATIONS IN EUROPE |
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In anticipation of the pending European marketing approval for Naglazyme™,
commercial operations have been established in Europe. BioMarin Europe Ltd.,
headquartered in London, with branch offices located in Spain, Switzerland
and Italy, will be responsible for overseeing the sales and distribution
of Naglazyme to the 25 member states of the European Union, Iceland and
Norway. |
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BIOMARIN FILES NEW DRUG APPLICATION FOR ORAPRED ODT |
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In August, BioMarin submitted a New Drug Application to the FDA for Orapred
ODT™ (prednisolone sodium phosphate orally disintegrating tablets),
a new formulation of Orapred® (prednisolone sodium phosphate oral solution).
Prednisolone is commonly used to reduce inflammation seen in numerous medical
conditions including asthma, arthritis and cancer.
Orapred ODT may have the potential to provide individuals of all ages with
a new formulation of prednisolone that is convenient and easy to administer. |
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BIOMARIN LAUNCHES NAGLAZYME IN THE UNITED STATES |
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June-Naglazyme® is the first drug therapy independently developed
and commercialized by BioMarin. A team of U.S. based medical science liaisons
will be responsible for providing support to infusion centers and physicians
who administer Naglazyme. |
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BIOMARIN RECEIVES FDA APPROVAL FOR NAGLAZYME |
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May-Naglazyme®, represents BioMarin's first independently developed
and commercialized drug and the first FDA-approved treatment for MPS VI.
The drug was granted the orphan drug designation in the United States, which
confers seven years of market exclusivity. |
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BioMarin Forms Strategic Alliance With Serono
for the Development and Commercialization of Phenoptin and Phenylase |
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This agreement helps fund late-stage development of BioMarin's PKU and
6R-BH4 programs. The companies will equally share Phase 3 development costs
of Phenoptin and Phenylase for PKU and 6R-BH4 for the treatment of cardiovascular
indications. Additionally, Serono will provide BioMarin up to $232 million
in milestone payments in exchange for ex-U.S. commercialization rights (excluding
Japan). |
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BioMarin Acquires Rights to 6R-BH4
for the Treatment of Cardiovascular Indications |
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In May 2005, BioMarin announced a partnership with Daiichi Suntory Pharma
Co., Ltd. that gave the company exclusive worldwide rights (excluding Japan)
for the use of 6R-BH4 to treat cardiovascular indications. This was the
second agreement reached with Daiichi; the first, which was reached in November
2004, pertained to intellectual property, preclinical and clinical data
on 6R-BH4 for genetic disorders including PKU, and to manufacturing and
supply of 6R-BH4. |
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BioMarin Initiates Phase 3 Clinical Study
of Phenoptin for PKU |
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In April 2005, BioMarin initiated a Phase 3 clinical study designed
to evaluate the safety and efficacy of Phenoptin for the treatment of
PKU. Phenoptin has been designated an orphan drug in the United States
and Europe and assigned Fast Track status in the United States.
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| BioMarin Files Marketing Applications for
Naglazyme in the United States and Europe |
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In June 2004, BioMarin announced positive results of the Phase 3 clinical
trial of Naglayzme (galsulfase) for MPS VI, keeping the company on track
to file license applications in both the United States and European Union
by the close of the year.
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| BioMarin Advances Phenoptin for PKU
into Phase 2 Development |
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In 2004, BioMarin advanced Phenoptin™ (sapropterin dihydrochloride),
an investigational small-molecule oral therapeutic for the treatment of
phenylketonuria (PKU), from IND filing into Phase 2 development by the close
of the year. |
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| Aldurazyme for MPS I Approved
and Launched in the Unites States and Europe |
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In April and June 2003, respectively, the FDA and European Commission
(EC) granted marketing authorization for Aldurazyme--the first approved
enzyme replacement therapy for the treatment of MPS I. Aldurazyme received
FDA approval in just over five and a half years after the investigational
new drug application (IND) was filed. |
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BioMarin Initiates Clinical Trial of
Naglazyme for
MPS VI |
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At the onset of clinical development, Naglazyme® (galsulfase) for
MPS VI had been granted orphan drug and fast track designations by the U.S.
Food and Drug Administration (FDA). The company manufactured the investigational
enzyme at its cGMP manufacturing facility located near the large-scale facility
where it is being manufactured today.
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BioMarin Becomes a Publicly Traded Company (Nasdaq/SWX:BMRN) |
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In July 1999, BioMarin completed an initial public offering, raising $67.3
million. Since a large number of the early investors were based in Europe,
the company was listed on the Swiss SWX Exchange in addition to the Nasdaq
National Market. |
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BioMarin/Genzyme LLC Formed to Support
the Development and Commercialization of Aldurazyme |
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In September 1998, BioMarin and Genzyme Corporation established BioMarin/Genzyme
LLC, a 50/50 joint venture for the worldwide development and commercialization
of Aldurazyme for MPS I. Pursuant to the agreement, BioMarin is responsible
for manufacturing the product and Genzyme is responsible for its commercialization.
All expenses and profits and are shared equally between the companies. |
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BioMarin Initiates Clinical Trial of
Aldurazyme for
MPS I |
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In December 1997, BioMarin initiated the first clinical trial of Aldurazyme®
(laronidase) for the treatment of mucopolysaccharidosis I (MPS I). Dr. Emil
Kakkis, then a fellow at Harbor-UCLA Medical Center, was the study’s
principal investigator and Dr. Elizabeth Neufeld, Professor and Chair of
the Biological Chemistry Department at UCLA, was the advisor. Together,
Dr. Neufeld and Dr. Kakkis discovered how to produce a recombinant form
of alpha-L-iduronidase that was later evaluated in the clinic. |
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BioMarin Pharmaceutical Inc. Founded |
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With a $1.5 million investment from Glyko Biomedical Ltd., BioMarin was
open for business. The company s mission was to leverage its proprietary
enzyme technology to develop therapies for the treatment of numerous diseases
and conditions including genetic diseases, and burn and wound care. By the
close of the year, the company had raised an additional $11.3 million from
private investors. |
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