OBJECTIVES: In most developed countries, policies incentivize manufacturers to invest in developing orphan drugs (OD) as the return on investment is unlikely.  The objective of this study was to assess the overall performance of OD policies on development and revenue of OD.

METHODS: We identified on FDA website the yearly number of OD approved. We gathered revenue associated to OD from companies and individual products perspective through IMS sales database, Datamonitor reports, and companies’ websites and annual reports. We reviewed published OD forecasts. RESULTS: In the US, the number of yearly approved drugs grew from less than 5 per year before 2000 to more than 20 in the last 3 years. In 2012, the turnover of OD business reached US$ 83 billion. The growth of this part of the pharmaceutical market is very fast with a sales forecasting of US$ 127 billion in 2018 (153% compared to 2012). In 2010, 65 products generated more than US $100 million revenue, 39 more than US$500 million, and 24 more than US $1 billion. Seven leading companies generate from US$9.9 to 1.7 billion yearly revenue with OD portfolio, representing a large proportion of the company turnover. This represents a serious burden on health insurance budget in most countries and will obviously continue to be subject to serious cost-containment measures. CONCLUSIONS: OD incentive policies reached their objective by contributing to a large increase of number of OD approved. Revenue associated to OD raises the question of appropriateness of OD policies as some products are among the top selling products. There is a need to review the OD policies and ensure it contribute to enhance development of product that would have not reached the market without solid incentive. Some authors proposed to revise the prevalence threshold to define OD.