World health dilemmas: Orphan and rare diseases, orphan drugs and orphan patients

Abstract

According to global annual estimates hunger/malnutrition is the major cause of death (36 of 62 million). Cardiovascular diseases and cancer (5.44 of 13.43 million) are the major causes of death in developed countries, while lower respiratory tract infections, human immunodeficiency virus infection/acquired immunodeficiency syndrome, diarrhoeal disease, malaria and tuberculosis (10.88 of 27.12 million) are the major causes of death in developing countries with more than 70% of deaths occurring in children. The majority of approximately 800 million people with other rare diseases, including 100000 children born with thalassaemia annually receive no treatment. There are major ethical dilemmas in dealing with global health issues such as poverty and the treatment of orphan and rare diseases. Of approximately 50000 drugs about 10% are orphan drugs, with annual sales of the latter approaching 100 billion USD. In comparison, the annual revenue in 2009 from the top 12 pharmaceutical companies in Western countries was 445 billion USD and the top drug, atorvastatin, reached 100 billion USD. In the same year, the total government expenditure for health in the developing countries was 410 billion USD with only 6%-7% having been received as aid from developed countries. Drugs cost the National Health Service in the United Kingdom more than 20 billion USD or 10% of the annual health budget. Uncontrollable drug prices and marketing policies affect global health budgets, clinical practice, patient safety and survival. Fines of 5.3 billion USD were imposed on two pharmaceutical companies in the United States, the regulatory authority in France was replaced and clinicians were charged with bribery in order to overcome recent illegal practises affecting patient care. High expenditure for drug development is mainly related to marketing costs. However, only 2 million USD was spent developing the drug deferiprone (L1) for thalassaemia up to the stage of multicentre clinical trials. The criteria for drug development, price levels and use needs to be readdressed to improve drug safety and minimise costs. New global health policies based on cheaper drugs can help the treatment of many categories of orphan and rare diseases and millions of orphan patients in developing and developed countries.

Keywords: Deferasirox; Deferiprone; Deferoxamine; Global diseases; Iron overload; Orphan diseases; Orphan drugs; Orphan patients; Rare diseases; Thalassaemia; World health issues.

Figure 1

Ethical issues arising from the influence of pharmaceutical companies. A diagram of a theoretical model describing the marketing influence of pharmaceutical companies on various sectors and organisations in relation to new patented drugs and its effect on public spending.

Figure 2

The chemical structure of chelators in clinical use. The chemical structures of the three orphan iron chelating drugs (A-C) which are used for the treatment of iron overload in thalassaemia and two other chelators used in other conditions (D and E): (A) deferoxamine (DF); (B) deferiprone (L1), (C) deferasirox (DFRA), (D) ethylenediaminetetraacetic acid (EDTA) and (E) diethylenetriaminepentaacetic acid (DTPA).