BioMarin Pharmaceutical Inc. is an American

biotechnology Biotechnology is a multidisciplinary field that involves the integration of natural sciences and Engineering Science, engineering sciences in order to achieve the application of organisms and parts thereof for products and services. Specialists ...

company headquartered in

San Rafael, California San Rafael ( ; Spanish language, Spanish for "Raphael (archangel), St. Raphael", ) is a city in and the county seat of Marin County, California, United States. The city is located in the North Bay (San Francisco Bay Area), North Bay region of th ...

. It has offices and facilities in the

United States The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...

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, and

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. BioMarin's core business and research is in enzyme replacement therapies (ERTs). BioMarin was the first company to provide therapeutics for

mucopolysaccharidosis Mucopolysaccharidoses are a group of metabolic disorders caused by the absence or malfunctioning of lysosomal enzymes needed to break down molecules called glycosaminoglycans (GAGs). These long chains of sugar carbohydrates occur within the cel ...

type I (MPS I), by manufacturing laronidase (

Aldurazyme Iduronidase (, ''L-iduronidase'', ''α-L-iduronidase'', ''laronidase''), sold as Aldurazyme, is an enzyme with the systematic name ''glycosaminoglycan α-L-iduronohydrolase''. It catalyses the hydrolysis of unsulfated α-L-iduronosidic linkage ...

, commercialized by

Genzyme Genzyme (also known as Genzyme Transgenics Corp or GTC Biotherapeutics) was an American biotechnology company based in Cambridge, Massachusetts. From its acquisition in 2011 to 2022 Genzyme operated as a fully owned subsidiary of Sanofi. In 2010, ...

Corporation). BioMarin was also the first company to provide therapeutics for phenylketonuria (

PKU Phenylketonuria (PKU) is an inborn error of metabolism that results in decreased metabolism of the amino acid phenylalanine. Untreated PKU can lead to intellectual disability, seizures, behavioral problems, and mental disorders. It may also res ...

). Over the years, BioMarin has been criticised for drug pricing and for specific instances of denying access to drugs in clinical trials.

History

BioMarin was founded in 1997 by Christopher Starr Ph.D. and Grant W. Denison Jr. with an investment of a $1.5 million from Glyko Biomedical and went public in 1999. Seed investors were amongst others MPM Bioventures, Grosvenor Fund and Florian Schönharting.

Business development

In 2002, BioMarin acquired Glyko Biomedical. In 2009, BioMarin acquired Huxley Pharmaceuticals, Inc. (Huxley), which had rights to a proprietary form of

3,4-diaminopyridine Amifampridine phosphate is used as a drug, predominantly in the treatment of a number of rare muscle diseases. The free base form of the drug has been used to treat congenital myasthenic syndromes and approved by the FDA for Lambert–Eaton m ...

(3,4-DAP),

amifampridine phosphate Amifampridine phosphate is used as a drug, predominantly in the treatment of a number of rare muscle diseases. The free base form of the drug has been used to treat congenital myasthenic syndromes and approved by the FDA for Lambert–Eaton m ...

. In 2010, BioMarin was granted marketing approval by the

European Commission The European Commission (EC) is the primary Executive (government), executive arm of the European Union (EU). It operates as a cabinet government, with a number of European Commissioner, members of the Commission (directorial system, informall ...

for 3,4-diaminopyridine (3,4-DAP), amifampridine phosphate for the treatment of the rare autoimmune disease

Lambert–Eaton myasthenic syndrome Lambert–Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder characterized by muscle weakness of the limbs. It is also known as myasthenic syndrome, Eaton–Lambert syndrome, and when related to cancer, carcinomatous myopathy. ...

(LEMS). BioMarin launched the product under the name Firdapse. In 2010, BioMarin acquired LEAD Therapeutics, Inc. (LEAD), a small private drug discovery and early stage development company with key compound LT-673, an orally available poly (ADP-ribose) polymerase (PARP) inhibitor studied for the treatment of patients with rare, genetically defined cancers. This acquisition was followed by the purchase of ZyStor Therapeutics, Inc. (ZyStor), a privately held biotechnology company developing ERTs for the treatment of lysosomal storage disorders and its lead product candidate, ZC-701, a fusion of insulin-like growth factor 2 and alpha glucosidase (IGF2-GAA) in development for Pompe disease. At its R&D day in October 2010, BioMarin also announced a new program for a peptide therapeutic, vosoritide (BMN-111), for the treatment of

achondroplasia Achondroplasia is a genetic disorder with an autosomal dominant pattern of inheritance whose primary feature is dwarfism. It is the most common cause of dwarfism and affects about 1 in 27,500 people. In those with the condition, the Rhizomeli ...

. In 2012, BioMarin acquired Zacharon Pharmaceuticals, a private biotechnology company based in San Diego focused on developing small molecules targeting pathways of glycan metabolism. In 2014, BioMarin acquired a

histone deacetylase inhibitor Histone deacetylase inhibitors (HDAC inhibitors, HDACi, HDIs) are chemical compounds that enzyme inhibitor, inhibit histone deacetylases. Since acetylation of histones, deacetylation of histones produces transcriptionally silenced heterochromatin ...

chemical library A chemical library or compound library is a collection of stored chemicals usually used ultimately in high-throughput screening or industrial manufacture. The chemical library can consist in simple terms of a series of stored chemicals. Each chemi ...

from Repligen for $2 million with the intention of advancing work toward therapies for

Friedreich's ataxia Friedreich's ataxia (FRDA) is a rare, inherited, autosomal recessive neurodegenerative disorder that primarily affects the nervous system, causing progressive damage to the spinal cord, peripheral nerves, and cerebellum, leading to impaired ...

and other neurological disorders. In November 2014, the company agreed to the acquisition of Prosensa for up to $840 million; however, the range of treatments for

Duchenne muscular dystrophy Duchenne muscular dystrophy (DMD) is a severe type of muscular dystrophy predominantly affecting boys. The onset of muscle weakness typically begins around age four, with rapid progression. Initially, muscle loss occurs in the thighs and pe ...

failed to attain FDA approval, and development ceased in May 2016. In October 2019 it was revealed that the group will open an office in Dublin to support further growth through Europe, the Middle East and Asia.

Acquisition history

The following is an illustration of the company's major mergers and acquisitions and historical predecessors (this is not a comprehensive list):

Products

As of 2022, BioMarin has six products on the market, each of which is an

orphan drug An orphan drug is a medication, pharmaceutical agent that is developed to treat certain rare medical conditions. An orphan drug would not be profitable to produce without government assistance, due to the small population of patients affected by th ...

. *

Tetrahydrobiopterin Tetrahydrobiopterin (BH4, THB), also known as sapropterin ( INN), is a cofactor of the three aromatic amino acid hydroxylase enzymes, used in the metabolism of amino acid phenylalanine and in the biosynthesis of the neurotransmitters serotoni ...

(branded as Kuvan) (sapropterin dihydrochloride), a

small molecule In molecular biology and pharmacology, a small molecule or micromolecule is a low molecular weight (≤ 1000 daltons) organic compound that may regulate a biological process, with a size on the order of 1 nm. Many drugs are small molecules; ...

drug for

phenylketonuria Phenylketonuria (PKU) is an inborn error of metabolism that results in decreased metabolism of the amino acid phenylalanine. Untreated PKU can lead to intellectual disability, seizures, behavioral problems, and mental disorders. It may also r ...

, introduced in 2007 as the first medication-based intervention to treat

* Arylsulfatase B (branded as Naglazyme) (galsulfase), a

recombinant protein Protein production is the biotechnological process of generating a specific protein. It is typically achieved by the manipulation of gene expression in an organism such that it expresses large amounts of a recombinant gene. This includes the ...

therapeutic for Maroteaux–Lamy syndrome (also called mucopolysaccharidosis type VI) * Iduronidase (branded as Aldurazyme), a recombinant protein therapeutic for

I * Amifampridine (branded as Firdapse), a small molecule drug for

(as of 2013 approved in the EU only) * Elosulfase alfa (branded as Vimizim), is the only enzyme replacement therapy to address the cause of Morquio A Syndrome (MPS IVA), which affects an estimated 3,000 patients in the developed world. The disease occurs as a result of a deficiency of activity in an enzyme involved in glycosaminoglycan (GAG) metabolism. * Cerliponase alfa (branded as Brineura), is an enzyme replacement treatment for Batten disease, which is a form of neuronal ceroid lipofuscinosis. It was approved in 2017. *

Valoctocogene roxaparvovec Valoctocogene roxaparvovec, sold under the brand name Roctavian, is a gene therapy used for the treatment of hemophilia A. It was developed by BioMarin Pharmaceutical. Valoctocogene roxaparvovec is made of a virus (AAV5) that has been modified ...

(branded as Roctavian) is an adeno-associated viral vector for treatment of

hemophilia A Haemophilia A (or hemophilia A) is a blood clotting disorder caused by a genetic deficiency in clotting factor VIII, thereby resulting in significant susceptibility to bleeding, both internally and externally. This condition occurs almost exclu ...

that aims to transfer a working copy of the

Factor VIII Coagulation factor VIII (Factor VIII, FVIII, also known as anti-hemophilic factor (AHF)) is an essential blood clotting protein. In humans, it is encoded by ''F8'' gene. Defects in this gene result in hemophilia A, an X-linked bleeding disorder ...

gene into patients who lack one. It was approved in the EU in August 2022. Biomarin is working to develop several new drugs.

Controversies

In 2010, BioMarin became involved in controversy surrounding

(3,4-DAP). BioMarin markets a phosphate salt of 3,4-DAP under the name Firdapse. In 2010, BioMarin was granted exclusive licensing rights to Firdapse for 10 years. As a result, the price of a prescribed

National Health Service The National Health Service (NHS) is the term for the publicly funded health care, publicly funded healthcare systems of the United Kingdom: the National Health Service (England), NHS Scotland, NHS Wales, and Health and Social Care (Northern ...

treatment course has increased from $1,987 for the unlicensed drug to $69,970 for Firdapse. The company states that prior to its licensing, there was no guaranteed quality control of the product and no way of formally monitoring for uncommon side effects through the regulatory process. In 2013, BioMarin Pharmaceuticals was at the center of a high profile debate regarding

expanded access Expanded access or compassionate use is the use of an unapproved drug or medical device under special forms of investigational new drug, investigational new drug applications (IND) or Investigational device exemption, IDE application for devices, o ...

of cancer patients to experimental drugs. On the advice of her doctor, Andrea Sloan, a patient with advanced ovarian cancer, requested that the company provide her with access to BMN 673, an unapproved

PARP inhibitor PARP inhibitors are a class of drugs that are a group of pharmacological inhibitors of the enzyme poly ADP ribose polymerase (PARP), which plays a role in repairing DNA in damaged cells. Medical uses of these drugs include the treatment of heri ...

drug candidate that had exhibited promising activity in a small Phase 1 clinical trial. The company declined, citing safety concerns. Ms. Sloan eventually received a similar drug candidate from a different company. In 2015, there was another controversy over

, concerning the supply of a drug on clinical trial to a German child who was suffering from a brain disorder but who was not part of the trial. In April 2019, the BBC reported that patients who took part in a trial treatment for the drug Kuvan (sapropterin hydrochloride) were later denied access to it. The company was criticised by the NHS and Stephen Hammond MP for patient profiteering. The company commented the following in response: "BioMarin is disappointed that the NHS England has not recognised the value of treating PKU patients with Kuvan, despite more than a decade of positive patient outcomes across 26 countries in Europe, Russia and Turkey" In June 2019, a Belgian court ordered BioMarin to continue supplying Vimizim to a young girl suffering from Morquio syndrome free of charge. BioMarin stopped providing free Vimizim at the beginning of the year after negotiations with Belgian health authorities regarding

reimbursement Reimbursement is the act of compensating someone for an out-of-pocket expense by giving them an amount of money equal to what was spent. Companies, governments and nonprofit organizations may compensate their employees or officers for necessary ...

of the product repeatedly failed. This caused the parents to start

legal proceeding Legal proceeding is an activity that seeks to invoke the power of a tribunal in order to enforce a law. Although the term may be defined more broadly or more narrowly as circumstances require, it has been noted that " e term ''legal proceedings ...

s to force the company to keep providing the medicine free of charge. BioMarin was ordered in a

preliminary injunction An injunction is an equitable remedy in the form of a special court order compelling a party to do or refrain from doing certain acts. It was developed by the English courts of equity but its origins go back to Roman law and the equitable reme ...

to keep doing so until a definitive judgment would be rendered, or until the medicine would be available on the Belgian market at a reasonable price.

References

External links

* {{DEFAULTSORT:Biomarin Pharmaceutical Biotechnology companies of the United States Pharmaceutical companies of the United States Companies listed on the Nasdaq Technology companies based in the San Francisco Bay Area Companies based in San Rafael, California American companies established in 1997 Pharmaceutical companies established in 1997 Life sciences industry Biotechnology companies established in 1997 1997 establishments in California 1999 initial public offerings Virotherapy Health care companies based in California Companies in the S&P 400