A lack of incentives and poor documentation seem to contribute to the limited number of orphan medicinal products (OMPs) approved in the European Union, a paper in the March issue of the British Journal of Clinical Pharmacology concludes.
European legislation introduced in August 2000 aimed to encourage manufacturers to develop new medicines for the 5000 or so orphan diseases (those conditions with a prevalence of 5 cases per 10,000 of the population or less). Under the legislation, companies receive 10 years of marketing exclusivity, scientific advice to optimise development, reduced fees and a number of other incentives. However, unlike some other jurisdictions, the EU offers neither grants-in-aid nor tax breaks to encourage orphan drug development.
Between 1995 and August 2000, European regulators approved 12 orphan drugs. This increased to just 18 between August 2000 and December 2004, although the EMEA had designated 255 drugs as OMPs, according to Silvio Garattini and colleagues at the Mario Negri Institute for Pharmacological Research, Milan. This approval rate (7.1%) is less than a tenth that for the EMEA overall. Between August 2000 and December 2004, the EMEA approved 153 of the 193 general marketing authorisation applications (79.3%). The withdrawal rates for OMPs and overall authorisations were 43.7% and 18.2% respectively.
An accompanying editorial by Jeffrey Aronson of the Radcliffe Infirmary Oxford, contrasts the European approval rate with the situation in the USA. Between 1983 and 2002, the FDA designated nearly 1100 drugs and biologicals orphan products and approved 231 (21%) OMPs. Aronson speculates that lack of incentives in the EU may contribute to the discrepancy. Furthermore, he notes that the current NICE threshold (£30,000 per Quality Adjusted Life Year) may mean that treating rare diseases is not cost-effective. Aronson also calls for a comparison of dossiers in the two jurisdictions to identify other reasons that may contribute to the discrepancy in approval rates between the EU and USA.
Certainly, Garattini and colleagues identified several limitations in many of the dossiers of OMPs approved by the EMEA including, in many cases: too few dose-finding, controlled and active comparator studies; insufficient exposure to the drug; and use of surrogate end points. In the meantime, the Milan group adds that “the paucity of European funds for companies willing to develop OMP” contributed to the low rates of licences and the poor quality of the dossiers. They call for a special fund and tax relief for OMP sponsors.
Without better support of OMP development, thousands of people will continue to endure morbidity and mortality from rare diseases. As Garattini and colleagues conclude: “The fact that it took four years to develop 18 drugs and that there are still several thousand rare diseases awaiting therapy is a public health issue that cannot be neglected.”