European Commission publishes report on the availability of orphan medicines in the EU

The European Commission has published a major review on the availability and incentive mechanisms for the development of orphan medicines in the European Union (EU). The report is available to read in full here. The commission highlights 117 rare-disease medicines which have received market authorisation since the adoption of centralised marketing-authorization procedure for all orphan products in 2005 (see Europe: 13 January 2016: Number of new orphan-drug recommendations by the EMA rises to 18 in 2015). However, only 1% of rare diseases are currently covered by authorised medicines. Orphan-drug status is granted to compounds developed for the treatment of rare diseases that occur in a maximum of 5 per 10,000 people in the population. The European Commission estimates that as of 2016 there are between 5,000–8,000 rare diseases in the EU affecting between 27 and 37 million individuals (equivalent to about 6–8% of the total EU population). During the period 2000–2015, the European Medicines Agency (EMA) received 2,302 applications for orphan-drug status. Of these applications, the European Commission approved 1,544. These figures show that 1,227 orphan-drug designations still have active status in 2016, meaning that 317 have either lapsed or been withdrawn.

Significantly, the commission notes that oncology is by far the most frequently designated therapeutic area for orphan-disease medicines (about 36% in total); among the most prevalent sub-categories are indications for myeloid leukaemia, cystic fibrosis, glioma, pancreatic carcinoma, ovarian cancer, multiple myeloma, chronic lymphoblastic leukaemia, and hepatocellular carcinoma.

Upon receiving European Commission market-authorisation approval, orphan-drug manufacturers benefit from a 10-year period of patent protection. Market exclusivity can be extended by a further two years for paediatric approvals. Only two products for a paediatric indication have been competed: thrombocythaemia treatment Xagrid (anagrelide) and Tobi Podhaler (tobramycin inhalation powder) have an extended 12-year market exclusivity. According to the commission, the "most important incentive" is the 10-year market exclusivity, which the authors imply is a provision that should be maintained. In addition, a number of incentives – including a reduction in fees and scientific advice through the Committee for Medicinal Products for Human Use (CHMP) – are provided with the designation. The report largely considers that the current incentive system for orphan products is working effectively, as seen by the accelerating pace of rare-disease research and development (R&D) since 2009.

The commission also reports that the EMA has received a total of EUR78.4 million (USD85 million) from the EU budget over the previous 15 years to put towards reductions in fees for small and medium-sized enterprises (SMEs). Alongside approximately 951 assistance protocols for scientific advice (including 264 for SMEs), over the past 15 years the waiver of regulatory fees has helped to directly facilitate about 25 orphan marketing authorisations for smaller and medium-sized pharmaceutical developers. To that extent, the European Commission concludes that orphan-drug legislation has successfully addressed the issue of encouraging SMEs to develop rare-disease medicines. However, despite regulatory assistance, SMEs remain at a disadvantage by comparison with larger firms in terms of developing orphan drugs.

Apart from centralised efforts to improve access to orphan drugs, the report examines efforts by individual EU countries to ensure that patients benefit from these therapies, including by increasing budget allocations and engaging in risk-sharing agreements when faced with limited budgets.

Outlook and implications

The European Commission report concludes that orphan-medicine policy in the EU over the past 15 years has definitely boosted investment in the field. This is evidenced by the number of orphan-drug designations, which have been rising steadily on a year-on-year basis. However, the number of orphan-medicine approvals remains somewhat behind the comparable rate of approvals by the US FDA. Nevertheless, the European Commission supports the maintenance of existing incentives to encourage the development of "uneconomic" rare-disease medicines as essential for the pharmaceutical industry. This is encouraging for innovative pharmaceutical companies in Europe, which can expect to continue to benefit from strong incentive mechanisms for rare-drug initiatives and high treatment prices. The report does not consider the issues surrounding the increased use of special regulatory pathways to market authorisation for orphan-medicine products, such as the performance of expedited review procedures (designated fast-track, breakthrough status, priority review, accelerated approvals).