More than 40 orphan drugs have now been recommended for approval in the European Union since the regulation on orphan medicinal products came into force in August 2000.

The European Medicines Agency’s (EMEA) Committee for Medicinal Products for Human Use (CHMP) adopted its 40th and 41st positive opinions for orphan drugs at its plenary meeting on 18-21 June. The two products recommended for EU-wide approval were GlaxoSmithKline’s Atriance (nelarabine), for the treatment of T-cell acute lymphoblastic leukaemia (T-ALL) and T-cell lymphoblastic leukaemia (T-LBL); and Medac’s Gliolan (5-aminolevulinic hydrochloride), for the visualisation of malignant tissue during fluorescence-guided surgery for malignant glioma.

The oncology indications fit the pattern of orphan product recommendations in the EU since Regulation EC No 141/2000 introduced development incentives such as 10 years of marketing exclusivity, reductions in regulatory fees and free protocol assistance. Of the 41 orphan drugs that have so far been recommended for final approval by the European Commission, around 32% were for the treatment of rare cancers, 29% for metabolic conditions, 12% apiece for blood disorders and for diseases of the musculoskeletal and central nervous systems, and 10% for cardiovascular diseases.

Atriance was designated as an orphan medicinal product in June 2005 and Gliolan in November 2002. In all, more than 700 applications for orphan drug designation have been submitted in the EU since 2000. The EMEA’s Committee for Orphan Medicinal Products (COMP) has given a positive opinion in 470 of these cases and recommended refusal of orphan designation in just 11. The remaining applications were either withdrawn or are still being processed.

Last year saw 104 applications filed for orphan drug designation, compared with 118 in 2005. Of last year’s tally, 81 applications received a positive recommendation from the COMP (88 in 2005), 20 were withdrawn (30 in 2005), two (0) received negative opinions and 80 (88) were granted final orphan drug designation by the European Commission. At its 80th meeting on 26-27 June, the COMP adopted a further 10 positive opinions granting orphan drug status. That takes the score for 2007 to date up to 61 applications filed, 39 positive COMP opinions, no negative opinions, nine withdrawals and 28 designations granted by the Commission.

On top of this, the CHMP is currently reviewing another19 approval applications for designated orphan medicinal products. Since 2001, the EMEA notes, orphan drugs for more than 30 conditions and potentially benefiting some 1.6 million patients have been made available in the European Union.

Closing the gap

While these figures are undoubtedly encouraging, they only go some way towards closing the gap in orphan drug development with the United States, where more than 160 medicines have been approved for rare diseases since 1995, compared with 108 in the previous decade and fewer than 10 in the 1970s. As of January this year, 1,679 medicines had been designated as orphan products under the US Orphan Drug Act of 1983. Unlike the EU’s regulation, the US Act offers tax breaks in addition to its market exclusivity incentives.

Last year a paper in the British Journal of Clinical Pharmacology noted that just 18 products for rare diseases were approved in the EU between August 2000 and December 2004, despite the EMEA designating 255 drugs as orphan medicinal products (OMPs) during that period. While the authors identified a number of limitations in the dossiers for orphan drugs, they said the “paucity of European funds for companies willing to develop OMPs” was a factor in these deficiencies and the low rate of orphan approvals.

This year a total of €6 million (US$8.2 million) has been made available for orphan drug incentives through the EU’s special fund for OMPs.