OBJECTIVES: The development of orphan drugs (OD) has substantially increased in the last decade. The objective of this study was to describe the trends in OD approvals from 2002 to present in the United States. METHODS: We selected all OD approved between 2002 and 2013 from the FDA Orphan Products database. We extracted OD characteristics, especially all drug indications (with drug status as orphan/non orphan per therapeutic indication), the prevalence of the rare disease and the substance patent date. Frequency of approvals was described over time by therapeutic areas, prevalence of disease [rare vs. ultra rare (≤20 patients/million)] and duration of substance patent. Number of orphan indications by drug was also assessed over the last decade. RESULTS: Since 2002, 143 OD were approved with 162 indications for which the drugs were granted an orphan status (‘orphan indication’). The number of approved indications has increased by 76% when comparing 2011-2013 period to 2008-2010 period. Oncology was found to be the major indication area, accounting for 36% of overall indications, followed by gastroenterology (8%) and hematology (7%). Across all indication areas, OD approvals proportion in oncology remained relatively stable over time, while other areas appeared randomly distributed over the years. About 12% of OD was approved in 2 or more indications, with a stable number over time. Half of approved OD displayed less than 7 years patent protection, or the period of exclusivity granted by the Orphan Drug Act. Ultra OD indications represented 27% of overall approvals, with 41% of ultra orphan indications approved in the last 3 years. CONCLUSIONS: This analysis confirmed the increase of OD approvals with a substantial proportion in oncology area between 2002 and 2013. The 7 years exclusivity is critical for half of the products. No specific trends could be captured in the studied period.