Twenty-Four Years after launch of the EU Orphan Regulation: Analyzing Dutch Price Dynamics, Biosimilars and Generics for Orphan Medicinal Products.

Objectives: The Orphan Regulation, introduced in 2000, offers a ten-year exclusivity to recoup investments on orphan medicinal products (OMPs). Despite expectations of price drops, many OMPs seem to lack competition post-exclusivity. This study examines OMP price trends and the entry of generics/biosimilars in the Netherlands.

Methods: OMPs authorized before January 1, 2010, were included unless they had active substance patents or were withdrawn before the end of market exclusivity. Data on European generic/biosimilar authorization were gathered from the EMA and Dutch Medicines Evaluation Board. List price data were collected from the Dutch national database.

Results: Twenty-eight small molecules and nine biologicals were included in the primary analysis, all authorized between 14.0-22.3 years. The median of their most recent prices in the Netherlands was 81% of the initial price (range 11-104%). Eleven small molecule (39%) and eight biological (89%) OMPs did not have a generic/biosimilar registered. If generic/biosimilar entry did occur, this was after a median of 14.2 years (range 11.5-20.3 years). Median prices of OMPs with generic/biosimilar competition were lower than those without (to 66% versus 88% of the initial price, respectively, p < 0.01).

Conclusions: Post-exclusivity competition and subsequent price decrease is limited for OMPs. First, generics/biosimilars for OMPs enter later than non-OMPs. Second, for some OMPs (especially biologicals) there is no competition at all. Third, prices of OMPs with generic/biosimilar competition decreased only minimally compared to non-OMPs. New policies are needed to correct this apparent market failure.