Orphan drug

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.

Industry involvement

Key orphan drug developers including Swedish Orphan Biovitrum, 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. Key industry partnerships are being formed across global borders with a greater number of orphan disease indications being designated approval on a daily basis.

The annual industry World Orphan Drug Congress takes place in Geneva, Switzerland showcasing the opportunities and partnerships evolving in this industry.

Orphan drug law

The Orphan Drug Act (ODA) of January 1983, passed in the United States, with lobbying from the National Organization for Rare Disorders, 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 incentives. The European Union (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. The EU's legislation is administered by the Committee on Orphan Medicinal Products of the European Medicines Agency (EMA). 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. Orphan drug legislation also exists in Australia and Japan.

Under the ODA and EU legislation, many orphan drugs have been developed, including drugs to treat glioma, multiple myeloma, cystic fibrosis, phenylketonuria, snake venom poisoning, and idiopathic thrombocytopenic purpura. 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. Nevertheless, 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.

Television historian and Allmovie contributor Hal Erickson credits two episodes of the television series Quincy, M.E. for helping the ODA pass in the USA: "Seldom Silent, Never Heard" (1981) and "Give Me Your Weak" (1982). The show's star, Jack Klugman, even testified before Congress concerning the orphan drug issue.

Orphan drug development

Orphan drugs generally follow the same regulatory development path as any other pharmaceutical product, in which testing focuses on 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. Free market advocates often respond that without government-mandated minimum safety and efficacy requirements, drug development costs would be considerably lower.

The intervention by government on behalf of orphan drug development can take a variety of forms:

• Tax incentives.
• Enhanced patent protection and marketing rights.
• Clinical research financial subsidization.
• Creating a government-run enterprise to engage in research and development (see Crown corporation).

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 discovered every week and many have no treatments available. Currently, 350 orphan drugs have been approved for sale in the US.

See also

• Drug development
• European Organization for Rare Diseases
• Orphan disease
• Supplementary protection certificate

External links

• 2010 World Orphan Drug Congress
• Drug Information Association (DIA)
• EVENT: DIA/FDA Orphan Drug Designation Workshop November 2010
• European Commission - 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
• Orphan drugs regulation and market figures