BioMarin Pharmaceutical Inc. is an American

biotechnology Biotechnology is the integration of natural sciences and engineering sciences in order to achieve the application of organisms, cells, parts thereof and molecular analogues for products and services. The term ''biotechnology'' was first used b ...

company headquartered in

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

. It has offices and facilities in the

United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territorie ...

South America South America is a continent entirely in the Western Hemisphere and mostly in the Southern Hemisphere, with a relatively small portion in the Northern Hemisphere at the northern tip of the continent. It can also be described as the southe ...

Asia Asia (, ) is one of the world's most notable geographical regions, which is either considered a continent in its own right or a subcontinent of Eurasia, which shares the continental landmass of Afro-Eurasia with Africa. Asia covers an area ...

, and

Europe Europe is a large peninsula conventionally considered a continent in its own right because of its great physical size and the weight of its history and traditions. Europe is also considered a Continent#Subcontinents, subcontinent of Eurasia ...

. 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 lysosome, lysosomal enzymes needed to break down molecules called glycosaminoglycans (GAGs). These long chains of sugar carbohydrates occur within ...

type I (MPS I), by manufacturing laronidase (

Aldurazyme Iduronidase (, ''L-iduronidase'', ''alpha-L-iduronidase'', ''laronidase''), sold as Aldurazyme, is an enzyme with the systematic name ''glycosaminoglycan alpha-L-iduronohydrolase''. This enzyme catalyses the hydrolysis of unsulfated alpha-L-idu ...

, commercialized by

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

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 resu ...

). 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 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 Lambert–Eaton myasthenic syndrome (LEMS) through com ...

(3,4-DAP),

amifampridine phosphate Amifampridine 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 Lambert–Eaton myasthenic syndrome (LEMS) through co ...

. In 2010, BioMarin was granted marketing approval by the

European Commission The European Commission (EC) is the executive of the European Union (EU). It operates as a cabinet government, with 27 members of the Commission (informally known as "Commissioners") headed by a President. It includes an administrative body o ...

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. Around 60% of those with LEMS have an underlying malignancy, most commonly small-cell lung cancer; it is therefore regarded ...

(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 Vosoritide, sold under the brand name Voxzogo, is a medication used for the treatment of achondroplasia. The most common side effects include injection site reactions (such as swelling, redness, itching, or pain), vomiting, and decreased blood p ...

(BMN-111), for the treatment of

achondroplasia Achondroplasia is a genetic disorder with an autosomal dominant pattern of inheritance whose primary feature is dwarfism. In those with the condition, the arms and legs are short, while the torso is typically of normal length. Those affected ha ...

. 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 inhibit histone deacetylases. HDIs have a long history of use in psychiatry and neurology as mood stabilizers and anti-epileptics. More recently they are bei ...

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 chemic ...

from

Repligen Repligen is an American company devoted to the development and production of materials used in the manufacture of biological drugs. The company is based in Waltham, Massachusetts, and incorporated in Delaware in 1981. A public company, Repli ...

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

Friedreich's ataxia Friedreich's ataxia (FRDA or FA) is an autosomal-recessive genetic disease that causes difficulty walking, a loss of sensation in the arms and legs, and impaired speech that worsens over time. Symptoms generally start between 5 and 20 year ...

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 that primarily affects boys. Muscle weakness usually begins around the age of four, and worsens quickly. Muscle loss typically occurs first in the thighs and pelvis fol ...

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 pharmaceutical agent developed to treat medical conditions which, because they are so rare, would not be profitable to produce without government assistance. The conditions are referred to as orphan diseases. The assignment of ...

. *

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

(branded as Kuvan) (sapropterin dihydrochloride), a

small molecule Within the fields of 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 ar ...

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 resu ...

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

Arylsulfatase B Arylsulfatase B (N-acetylgalactosamine-4-sulfatase, chondroitinsulfatase, chondroitinase, acetylgalactosamine 4-sulfatase, N-acetylgalactosamine 4-sulfate sulfohydrolase, ) is an enzyme associated with mucopolysaccharidosis VI (Maroteaux–L ...

(branded as Naglazyme) (galsulfase), a

recombinant protein Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be fou ...

therapeutic for

Maroteaux–Lamy syndrome Maroteaux–Lamy syndrome, or Mucopolysaccharidosis Type VI (MPS-VI), is an inherited disease caused by a deficiency in the enzyme arylsulfatase B (ARSB). ASRB is responsible for the breakdown of large sugar molecules called glycosaminoglycans (G ...

(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 Elosulfase alfa (trade name Vimizim) is a drug for the treatment of Morquio syndrome which is caused by a deficiency in the enzyme N-acetylgalactosamine-6-sulfatase. Elosulfase alfa is a synthetic version of this enzyme. Elosulfase alfa was deve ...

(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 Cerliponase alfa, marketed as Brineura, is an enzyme replacement treatment for Batten disease, a neurodegenerative lysosomal storage disease. Specifically, Cerliponase alfa is meant to slow loss of motor function in symptomatic children over thre ...

(branded as Brineura), is an enzyme replacement treatment for

Batten disease Batten disease is a fatal disease of the nervous system that typically begins in childhood. Onset of symptoms is usually between 5 and 10 years of age. Often, it is autosomal recessive. It is the common name for a group of disorders called the n ...

, which is a form of

neuronal ceroid lipofuscinosis Neuronal ceroid lipofuscinosis is the general name for a family of at least eight genetically separate neurodegenerative lysosomal storage diseases that result from excessive accumulation of lipopigments (lipofuscin) in the body's tissues. These l ...

. 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 t ...

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

hemophilia A Haemophilia A (or hemophilia A) is a genetic deficiency in clotting factor VIII, which causes increased bleeding and usually affects males. In the majority of cases it is inherited as an X-linked recessive trait, though there are cases which arise ...

that aims to transfer a working copy of the

Factor VIII Factor VIII (FVIII) is an essential blood-clotting protein, also known as anti-hemophilic factor (AHF). In humans, factor VIII is encoded by the ''F8'' gene. Defects in this gene result in hemophilia A, a recessive X-linked coagulation 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 umbrella term for the publicly funded healthcare systems of the United Kingdom (UK). Since 1948, they have been funded out of general taxation. There are three systems which are referred to using the " ...

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 applications (IND) or IDE application for devices, outside of a clinical trial, by people with serious or life ...

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 group of pharmacological inhibitors of the enzyme poly ADP ribose polymerase (PARP). They are developed for multiple indications, including the treatment of heritable cancers. Several forms of cancer are more dependent on ...

drug candidate that had exhibited promising activity in a small

Phase 1 clinical trial The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases ...

. 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 Stephen or Steven is a common English first name. It is particularly significant to Christians, as it belonged to Saint Stephen ( grc-gre, Στέφανος ), an early disciple and deacon who, according to the Book of Acts, was stoned to death; h ...

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 Morquio syndrome, also known as Mucopolysaccharidosis Type IV (MPS IV), is a rare metabolic disorder in which the body cannot process certain types of sugar molecules called glycosaminoglycans (AKA GAGs, or mucopolysaccharides). In Morquio syndr ...

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 a ...

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'' i ...

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

preliminary injunction An injunction is a legal and equitable remedy in the form of a special court order that compels a party to do or refrain from specific acts. ("The court of appeals ... has exclusive jurisdiction to enjoin, set aside, suspend (in whole or in par ...

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 Orphan drug companies Life sciences industry Biotechnology companies established in 1997 1997 establishments in California 1999 initial public offerings Virotherapy Health care companies based in California