Orphan drug
Encyclopedia
An orphan drug is a pharmaceutical agent
that has been developed specifically to treat a rare medical condition, the condition itself being referred to as an orphan disease
. The assignment of orphan status to a disease and to any drugs developed to treat it is a matter of public policy
in many countries, and has resulted in medical breakthroughs that may not have otherwise been achieved due to the economics of drug research and development. In the US and EU it is easier to gain marketing approval for an orphan drug, and there may be other financial incentives such as extended exclusivity periods.
pharmacokinetics
and pharmacodynamics
, dosing
, stability, safety and efficacy. However, some statistical burdens are lessened in an effort to maintain development momentum. For example, orphan drug regulations generally acknowledge the fact that it may not be possible to test 1,000 patients in a phase III clinical trial, as fewer than that number may be afflicted with the disease in question.
Since the market for any drug with such a limited application scope would, by definition, be small and thus largely unprofitable, government intervention is often required to motivate a manufacturer to address the need for an orphan drug. Critics of free market enterprise
often cite this as a failure
of free market economic
systems.
The intervention by government on behalf of orphan drug development can take a variety of forms:
, with lobbying from the National Organization for Rare Disorders
and many other organizations, is meant to encourage pharmaceutical companies
to develop drugs for diseases that have a small market. Under the law, companies that develop such a drug (a drug for a disorder affecting fewer than 200,000 people in the United States) may sell it without competition for seven years, and may get clinical trial
tax incentive
s.
Orphan drug designation means that the sponsor qualifies for certain benefits, such as reduced taxes, from the federal government. It does not mean the drug is safe and effective and legal to manufacture and market in the United States.
to establish the Office of Rare Diseases. It also increased funding for the development of treatments for patients with rare diseases.
(EU) has enacted similar legislation, REGULATION (EC) No 141/2000, in which pharmaceuticals developed to treat rare diseases are referred to as "orphan medicinal products." The EU's definition of an orphan condition is broader than that of the USA, in that it also covers some tropical diseases that are primarily found in developing nations. Orphan drug status granted by the European Commission gives marketing exclusivity in the EU for 10 years after approval. The EU's legislation is administered by the Committee on Orphan Medicinal Products of the European Medicines Agency
(EMA).
, multiple myeloma
, cystic fibrosis
, phenylketonuria
, snake venom
poisoning, and idiopathic thrombocytopenic purpura
.
The ODA is nearly universally acknowledged to be a success. Before Congress enacted the ODA in 1983 only 38 drugs were approved in the USA specifically to treat orphan diseases. In the USA, from January 1983 to June 2004, a total of 1,129 different orphan drug designations have been granted by the Office of Orphan Products Development (OOPD) and 249 orphan drugs have received marketing authorization. In contrast, the decade prior to 1983 saw fewer than ten such products come to market. From the passage of the ODA in 1983 until May 2010, the FDA approved 353 orphan drugs and granted orphan designations to 2,116 compounds. As of 2010, 200 of the roughly 7,000 officially designated orphan diseases have become treatable. Some critics have questioned whether orphan drug legislation was the real cause of this increase (claiming that many of the new drugs were for disorders that were already being researched anyway, and would have had drugs developed regardless of the legislation), and whether the ODA has really stimulated the production of truly non-profitable drugs; the act also received some criticism for allowing some pharmaceutical companies to make a large profit off of drugs that have a small market but still sell for a high price.
Although the European Medicines Agency
grants market access its 27 member states, in practice, medicines only reach the market when each member state decides that its national health system will reimburse for the drug. For example, 35 orphan drugs reached the market in Belgium, 44 in the Netherlands, and 28 in Sweden in 2008. 35 such drugs reached the market in France and 23 in Italy in 2007.
is presently considered the rarest genetic disease. No single cutoff number has been agreed upon for which a disease is considered rare. A disease may be considered rare in one part of the world, or in a particular group of people, but still be common in another.
Research has found that as many as one-in-ten Americans suffers from rare disease. Over 55 million people are estimated to suffer from a rare disease in Europe and in the US. Global estimates are between 5000 to 7000 rare diseases. New rare diseases are discovered every week and many have no treatments available. Currently, 350 orphan drugs have been approved for sale in the US.
was developed to treat Wilson's Disease, a rare hereditary disease that can lead to a fatal accumulation of copper in the body. This drug was later found to be effective in treating arthritis.
, Global Genes Project
, Children's Rare Disease Network, Abetalipoproteinemia Collaboration Foundation, Zellweger Baby Support Network, and the Friedreich's Ataxia Research Alliance have been founded in order to advocate on behalf of patients suffering from rare diseases with a particular emphasis on diseases that afflict children.
, Shire plc, GlaxoSmithKline
, Pfizer
, Novartis
, Genzyme
, Lundbeck
and BioMarin
are leading the way in this growing industry. These pharmaceutical companies work together with national bodies such as the U.S.'s National Organization for Rare Disorders
(NORD) and the European Organization for Rare Diseases
(EURORDIS) to advance this field.
College of Pharmacy provides help to small companies with insufficient in-house expertise and resources in the areas of drug synthesis, formulation, pharmacometrics, and bio-analysis.
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
that has been developed specifically to treat a rare medical condition, the condition itself being referred to as an orphan disease
Rare disease
A rare disease, also referred to as an orphan disease, is any disease that affects a small percentage of the population.Most rare diseases are genetic, and thus are present throughout the person's entire life, even if symptoms do not immediately appear...
. The assignment of orphan status to a disease and to any drugs developed to treat it is a matter of public policy
Public policy (law)
In private international law, the public policy doctrine or ordre public concerns the body of principles that underpin the operation of legal systems in each state. This addresses the social, moral and economic values that tie a society together: values that vary in different cultures and change...
in many countries, and has resulted in medical breakthroughs that may not have otherwise been achieved due to the economics of drug research and development. In the US and EU it is easier to gain marketing approval for an orphan drug, and there may be other financial incentives such as extended exclusivity periods.
Orphan drug legislation
Orphan drugs generally follow the same regulatory development path as any other pharmaceutical product, in which testing focuses onpharmacokinetics
Pharmacokinetics
Pharmacokinetics, sometimes abbreviated as PK, is a branch of pharmacology dedicated to the determination of the fate of substances administered externally to a living organism...
and pharmacodynamics
Pharmacodynamics
Pharmacodynamics is the study of the biochemical and physiological effects of drugs on the body or on microorganisms or parasites within or on the body and the mechanisms of drug action and the relationship between drug concentration and effect...
, dosing
Dosing
Dosing generally applies to feeding chemicals or medicines in small quantities into a process fluid or to a living being at intervals or to atmosphere at intervals to give sufficient time for the chemical or medicine to react or show the results....
, stability, safety and efficacy. However, some statistical burdens are lessened in an effort to maintain development momentum. For example, orphan drug regulations generally acknowledge the fact that it may not be possible to test 1,000 patients in a phase III clinical trial, as fewer than that number may be afflicted with the disease in question.
Since the market for any drug with such a limited application scope would, by definition, be small and thus largely unprofitable, government intervention is often required to motivate a manufacturer to address the need for an orphan drug. Critics of free market enterprise
Free market
A free market is a competitive market where prices are determined by supply and demand. However, the term is also commonly used for markets in which economic intervention and regulation by the state is limited to tax collection, and enforcement of private ownership and contracts...
often cite this as a failure
Market failure
Market failure is a concept within economic theory wherein the allocation of goods and services by a free market is not efficient. That is, there exists another conceivable outcome where a market participant may be made better-off without making someone else worse-off...
of free market economic
Economics
Economics is the social science that analyzes the production, distribution, and consumption of goods and services. The term economics comes from the Ancient Greek from + , hence "rules of the house"...
systems.
The intervention by government on behalf of orphan drug development can take a variety of forms:
- TaxTaxTo tax is to impose a financial charge or other levy upon a taxpayer by a state or the functional equivalent of a state such that failure to pay is punishable by law. Taxes are also imposed by many subnational entities...
incentives. - Enhanced patentPatentA patent is a form of intellectual property. It consists of a set of exclusive rights granted by a sovereign state to an inventor or their assignee for a limited period of time in exchange for the public disclosure of an invention....
protection and marketing rights. - Clinical research financial subsidization.
- Creating a government-run enterprise to engage in research and development (see Crown corporation).
Orphan Drug Act
The Orphan Drug Act (ODA) of January 1983, passed in the United StatesUnited States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
, with lobbying from the National Organization for Rare Disorders
National Organization for Rare Disorders
The National Organization for Rare Disorders is an American non-profit organization aiming to provide support individuals with rare diseases by advocating and funding research, education, and networking among service providers...
and many other organizations, is meant to encourage pharmaceutical companies
Pharmaceutical company
The pharmaceutical industry develops, produces, and markets drugs licensed for use as medications. Pharmaceutical companies are allowed to deal in generic and/or brand medications and medical devices...
to develop drugs for diseases that have a small market. Under the law, companies that develop such a drug (a drug for a disorder affecting fewer than 200,000 people in the United States) may sell it without competition for seven years, and may get clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
tax incentive
Tax incentive
A tax incentive is an aspect of the tax code designed to incentivize, or encourage, a certain type of behavior. This may be accomplished through means including tax holidays, tax deductions, or tax abatements...
s.
Orphan drug designation means that the sponsor qualifies for certain benefits, such as reduced taxes, from the federal government. It does not mean the drug is safe and effective and legal to manufacture and market in the United States.
Rare Diseases Act
In 2002 President George W. Bush signed the Rare Diseases Act into law. This legislation amended the Public Health Service ActPublic Health Service Act
The Public Health Service Act is a United States federal law enacted in 1944. The full act is captured under Title 42 of the United States Code "The Public Health and Welfare", Chapter 6A "Public Health Service"....
to establish the Office of Rare Diseases. It also increased funding for the development of treatments for patients with rare diseases.
European Union
The European UnionEuropean Union
The European Union is an economic and political union of 27 independent member states which are located primarily in Europe. The EU traces its origins from the European Coal and Steel Community and the European Economic Community , formed by six countries in 1958...
(EU) has enacted similar legislation, REGULATION (EC) No 141/2000, in which pharmaceuticals developed to treat rare diseases are referred to as "orphan medicinal products." The EU's definition of an orphan condition is broader than that of the USA, in that it also covers some tropical diseases that are primarily found in developing nations. Orphan drug status granted by the European Commission gives marketing exclusivity in the EU for 10 years after approval. The EU's legislation is administered by the Committee on Orphan Medicinal Products of the European Medicines Agency
European Medicines Agency
The European Medicines Agency is a European agency for the evaluation of medicinal products. From 1995 to 2004, the European Medicines Agency was known as European Agency for the Evaluation of Medicinal Products.Roughly parallel to the U.S...
(EMA).
Regulatory harmonization
In an effort to reduce the burden on manufacturers applying for orphan drug status, the FDA and EMA agreed in late 2007 to utilize a common application process for both agencies. However, the two agencies will continue to maintain separate approval processes.Other countries
In addition to the United States and the European Union, legislation has been implemented by Japan, Singapore, and Australia have all passed legislation that offers subsidies and other incentives to encourage the development of drugs that treat orphan diseases.Effectiveness
Under the ODA and EU legislation, many orphan drugs have been developed, including drugs to treat gliomaGlioma
A glioma is a type of tumor that starts in the brain or spine. It is called a glioma because it arises from glial cells. The most common site of gliomas is the brain.-By type of cell:...
, multiple myeloma
Multiple myeloma
Multiple myeloma , also known as plasma cell myeloma or Kahler's disease , is a cancer of plasma cells, a type of white blood cell normally responsible for the production of antibodies...
, cystic fibrosis
Cystic fibrosis
Cystic fibrosis is a recessive genetic disease affecting most critically the lungs, and also the pancreas, liver, and intestine...
, phenylketonuria
Phenylketonuria
Phenylketonuria is an autosomal recessive metabolic genetic disorder characterized by a mutation in the gene for the hepatic enzyme phenylalanine hydroxylase , rendering it nonfunctional. This enzyme is necessary to metabolize the amino acid phenylalanine to the amino acid tyrosine...
, snake venom
Snake venom
Snake venom is highly modified saliva that is produced by special glands of certain species of snakes. The glands which secrete the zootoxin are a modification of the parotid salivary gland of other vertebrates, and are usually situated on each side of the head below and behind the eye,...
poisoning, and idiopathic thrombocytopenic purpura
Idiopathic thrombocytopenic purpura
Idiopathic thrombocytopenic purpura is the condition of having an abnormally low platelet count of no known cause . As most incidents of ITP appear to be related to the production of antibodies against platelets, immune thrombocytopenic purpura or immune thrombocytopenia are terms also used to...
.
The ODA is nearly universally acknowledged to be a success. Before Congress enacted the ODA in 1983 only 38 drugs were approved in the USA specifically to treat orphan diseases. In the USA, from January 1983 to June 2004, a total of 1,129 different orphan drug designations have been granted by the Office of Orphan Products Development (OOPD) and 249 orphan drugs have received marketing authorization. In contrast, the decade prior to 1983 saw fewer than ten such products come to market. From the passage of the ODA in 1983 until May 2010, the FDA approved 353 orphan drugs and granted orphan designations to 2,116 compounds. As of 2010, 200 of the roughly 7,000 officially designated orphan diseases have become treatable. Some critics have questioned whether orphan drug legislation was the real cause of this increase (claiming that many of the new drugs were for disorders that were already being researched anyway, and would have had drugs developed regardless of the legislation), and whether the ODA has really stimulated the production of truly non-profitable drugs; the act also received some criticism for allowing some pharmaceutical companies to make a large profit off of drugs that have a small market but still sell for a high price.
Although the European Medicines Agency
European Medicines Agency
The European Medicines Agency is a European agency for the evaluation of medicinal products. From 1995 to 2004, the European Medicines Agency was known as European Agency for the Evaluation of Medicinal Products.Roughly parallel to the U.S...
grants market access its 27 member states, in practice, medicines only reach the market when each member state decides that its national health system will reimburse for the drug. For example, 35 orphan drugs reached the market in Belgium, 44 in the Netherlands, and 28 in Sweden in 2008. 35 such drugs reached the market in France and 23 in Italy in 2007.
Orphan diseases
A rare disease, also referred to as an "orphan disease," is any disease that affects a small percentage of the population. Most rare diseases are genetic, and thus are present throughout the person's entire life, even if symptoms do not immediately appear. Many rare diseases appear early in life, and about 30 percent of children with rare diseases will die before reaching their fifth birthday. With a single diagnosed patient only, ribose-5-phosphate isomerase deficiencyRibose-5-phosphate isomerase deficiency
Ribose-5-phosphate isomerase deficiency is a human disorder caused by mutations in the pentose phosphate pathway enzyme ribose-5-phosphate isomerase...
is presently considered the rarest genetic disease. No single cutoff number has been agreed upon for which a disease is considered rare. A disease may be considered rare in one part of the world, or in a particular group of people, but still be common in another.
Research has found that as many as one-in-ten Americans suffers from rare disease. Over 55 million people are estimated to suffer from a rare disease in Europe and in the US. Global estimates are between 5000 to 7000 rare diseases. New rare diseases are discovered every week and many have no treatments available. Currently, 350 orphan drugs have been approved for sale in the US.
Cystic fibrosis
In the 1980s, cystic fibrosis patients rarely lived beyond their early teens. However, drugs like Pulmozyme and Tobramycin, both developed with aid from the ODA, revolutionized treatment for cystic fibrosis patients by significantly improving their quality of life and extending their life expectancies. Now, cystic fibrosis patients often survive into their thirties and some into their fifties.Homozygous familial hypercholesterolemia
The 1985 Nobel Prize for medicine went to two researchers for their work related to homozygous familial hypercholesterolemia, an orphan disease that causes large and rapid increases in cholesterol levels. Their research led to the development of statin drugs that are commonly used to treat high cholesterol.Wilson's Disease
PenicillaminePenicillamine
Penicillamine is a pharmaceutical of the chelator class. It is sold under the trade names of Cuprimine and Depen. The pharmaceutical form is D-penicillamine, as L-penicillamine is toxic...
was developed to treat Wilson's Disease, a rare hereditary disease that can lead to a fatal accumulation of copper in the body. This drug was later found to be effective in treating arthritis.
Activism
Numerous advocacy groups such as the National Organization for Rare DisordersNational Organization for Rare Disorders
The National Organization for Rare Disorders is an American non-profit organization aiming to provide support individuals with rare diseases by advocating and funding research, education, and networking among service providers...
, Global Genes Project
Global Genes Project
The Global Genes Project is a grassroots project designed to raise rare disease awareness, and fund research to cure rare diseases.-History:The Global Genes Project , is a leading non-profit rare disease advocacy organization dedicated to raising awareness for the more than 7000 distinct rare...
, Children's Rare Disease Network, Abetalipoproteinemia Collaboration Foundation, Zellweger Baby Support Network, and the Friedreich's Ataxia Research Alliance have been founded in order to advocate on behalf of patients suffering from rare diseases with a particular emphasis on diseases that afflict children.
Industry involvement
Key orphan drug developers including Synageva BioPharma Corp., Swedish Orphan BiovitrumBiovitrum
Swedish Orphan Biovitrum is a Swedish pharmaceutical company, based in Stockholm, Sweden, with a product portfolio consisting of some 60 orphan and specialty pharmaceuticals.- History :...
, Shire plc, GlaxoSmithKline
GlaxoSmithKline
GlaxoSmithKline plc is a global pharmaceutical, biologics, vaccines and consumer healthcare company headquartered in London, United Kingdom...
, Pfizer
Pfizer
Pfizer, Inc. is an American multinational pharmaceutical corporation. The company is based in New York City, New York with its research headquarters in Groton, Connecticut, United States...
, Novartis
Novartis
Novartis International AG is a multinational pharmaceutical company based in Basel, Switzerland, ranking number three in sales among the world-wide industry...
, Genzyme
Genzyme
Genzyme Corporation is a fully owned subsidiary of Sanofi-Aventis. Before its acquisition, Genzyme was an American biotechnology company based in Cambridge, Massachusetts. In 2010, Genzyme was the world’s third-largest biotechnology company, employing more than 11,000 people around the world...
, Lundbeck
Lundbeck
H. Lundbeck A/S is a Danish international pharmaceutical company engaged in the research and development, production, marketing, and sale of drugs for the treatment of disorders in the central nervous system , including depression, schizophrenia, Alzheimer’s disease, Parkinson’s disease,...
and BioMarin
BioMarin Pharmaceutical
BioMarin Pharmaceutical Inc. is a biotechnology firm based in Novato, California. It has offices and facilities in the US, South America, Asia and Europe. BioMarin's core business and research is in enzyme replacement therapies...
are leading the way in this growing industry. These pharmaceutical companies work together with national bodies such as the U.S.'s National Organization for Rare Disorders
National Organization for Rare Disorders
The National Organization for Rare Disorders is an American non-profit organization aiming to provide support individuals with rare diseases by advocating and funding research, education, and networking among service providers...
(NORD) and the European Organization for Rare Diseases
European Organization for Rare Diseases
The European Organization for Rare Diseases is a non-governmental patient-driven alliance of patient organizations and individuals active in the field of rare diseases, that promotes research on rare diseases and commercial development of orphan drugs. EURORDIS is a dedicated to improving the...
(EURORDIS) to advance this field.
Center for Orphan Drug Research
The Center for Orphan Drug Research at the University of MinnesotaUniversity of Minnesota
The University of Minnesota, Twin Cities is a public research university located in Minneapolis and St. Paul, Minnesota, United States. It is the oldest and largest part of the University of Minnesota system and has the fourth-largest main campus student body in the United States, with 52,557...
College of Pharmacy provides help to small companies with insufficient in-house expertise and resources in the areas of drug synthesis, formulation, pharmacometrics, and bio-analysis.
Keck Graduate Institute Center for Rare Disease Therapies
The Keck Graduate Institute Center for Rare Disease Therapies (CRDT) in Claremont, California supports projects to revive potential orphan drugs whose development has stalled by identifying barriers to commercialization such as problems with formulation and bio-processing.See also
- Drug developmentDrug developmentDrug development is a blanket term used to define the process of bringing a new drug to the market once a lead compound has been identified through the process of drug discovery...
- European Organization for Rare DiseasesEuropean Organization for Rare DiseasesThe European Organization for Rare Diseases is a non-governmental patient-driven alliance of patient organizations and individuals active in the field of rare diseases, that promotes research on rare diseases and commercial development of orphan drugs. EURORDIS is a dedicated to improving the...
- Orphan disease
- Supplementary protection certificateSupplementary protection certificateIn European Union member countries, a supplementary protection certificate is a sui generis, extension of a patent under a specific, different, set of right. This type of right is available for medicinal products, such as drugs, and plant protection products, such as insecticides, and herbicides...
External links
- Drug Information Association (DIA)
- EVENT: DIA/FDA Orphan Drug Designation Workshop November 2010
- European CommissionEuropean CommissionThe European Commission is the executive body of the European Union. The body is responsible for proposing legislation, implementing decisions, upholding the Union's treaties and the general day-to-day running of the Union....
- The Orphan drugs strategy - List of European Orphan Drugs
- USA Food and Drug Administration: The Orphan Drug Act (as amended)
- US FDA List of Orphan Designations and Approvals