The orphan medicinal product regulation (Regulation (EC) No 141/2000) was adopted in December 1999 and came into force in the European Union (EU) in 2000. Nine years after its implementation, the Committee for Orphan Medicinal Products (COMP) will be celebrating its 100th meeting in April.
The Orphan Drug Regulation addresses the need to offer incentives for the development and marketing of drugs to treat, prevent, or diagnose rare conditions; without such incentives, the cost of developing and marketing products for these disorders would not be recovered by sales. The Regulation delineates the designation criteria, outlines the procedure for designation, and provides for incentives for products receiving an orphan designation. The incentives contained in the legislation aim to assist sponsors receiving orphan drug designations in the development of medicinal products with the ultimate goal of providing medicinal products for rare diseases to patients.
Orphan designation can be based on a number of factors: the prevalence of the condition; the return generated by the product too insufficient to justify investment; the severity of the condition; and the existence of alternative products. To receive designation, a product must target a life-threatening or chronically debilitating condition that affects no more than five in 10,000 persons (which currently corresponds to about 250,000 persons in the EU). Many rare conditions have a much lower prevalence.
Alternative to the rarity of the condition, sponsors can also apply if they are able to justify that without incentives the development costs of the product will not be recovered by the return obtained once the product is on the market. Any application for orphan drug designation must also describe all authorised methods of treatment (or diagnosis or prevention) existing for the orphan indication being applied for; in cases where authorised products already exist for the condition, the sponsor is asked to justify what the significant benefit would be for patients who would receive the proposed orphan product. What would be the clinically relevant advantage for patients if the proposed orphan product is marketed, or how would the drug contribute to their care? Normally this criterion is assessed at a very early stage in the drug development process, therefore at the time of designation the arguments are usually based on assumptions that will have to be confirmed at the time of marketing authorisation, when efficacy and safety data are available.
The EMEA is responsible for orphan drug designation through its Committee for Orphan Medicinal Products (COMP), which is comprised of health professionals representing each of the Member States, three patient representatives, and three representatives nominated by the EMEA. The Committee meets once a month and its responsibilities include the assessment of applications for orphan designation, the adoption of opinions on designation, advising the European Commission (EC) on policy relating to orphan medicines, assisting the EC in liaising internationally on matters relating to orphan medicinal products, and assisting the EC in drawing up detailed guidelines. The COMP is presently chaired by Professor Kerstin Westermark (Sweden) and co-chaired by Ms Birthe Byskov Holm (Patient Representative, Denmark). The COMP was pioneer in including patient representatives as full members and the experience has illustrated the great added-value of this collaboration, which contributes to the quality of the opinions adopted for orphan designation.
The achievements of the committee after 100 meetings can be summarised by the 634 positive opinions on orphan designation adopted so far from the 910 applications submitted for designation. The success rate for applications is almost 70%. The number of applications that currently receive orphan designation in 60 days, therefore without needing further clarification, is approximately 70%. With regard to the therapeutic areas attracting most designations, oncology has been the most represented with more than 40% of positive opinions on designation, followed by products for the musculoskeletal and nervous system (12%) and cardiovascular and respiratory systems (11%). Importantly, of the total number of positive opinions adopted, 64% are for conditions with prevalence lower than three in 10,000 persons. The Committee has received many applications for innovative products and has designated, amongst others, fusion proteins, monoclonal antibodies, cell and gene therapy products, and oligonucleotides to be developed for the treatment of rare diseases.
The development of orphan medicinal products is supported by incentives for development and placement on the market as provided for in the Orphan Regulation. Protocol Assistance, is provided by the Scientific Advice Working Party in collaboration with the COMP. Protocol assistance offers advice on the development of orphan drugs with regards to regulatory, quality, safety and efficacy issues.
The Committee is committed to continuing its work on orphan medicinal product designation and stimulating the development and placing on the market of such medicines. In the near future the COMP will be working on the preparation of the tenth anniversary of the adoption of the Regulation and on the assessment of its achievements.
