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Orphan drugs: medicine for the treatment of severe diseases

‘Orphan drugs’ are drugs for the treatment of rare, but severe diseases. There are about 5,000 such rare diseases, of which the majority (80 per cent) are genetic diseases.

Since the number of patients who need such drugs is very small, the pharmaceutical industry has naturally been reluctant to develop drugs for the treatment of rare diseases as they did not expect research and development investments to be amortised in a reasonable period of time. This has been even more the case since the 1970s. Drug development costs have risen continuously due to stricter regulations (as a result of the thalidomide catastrophe) and the merger of more and more companies to become larger global groups of companies.

Economic stimulus for the therapy of rare diseases

In order to prevent the existing gap in the drug supply for rarer diseases from becoming even larger, the United States Congress decided to put in place economic stimuli for the development of such drugs. The ‘Orphan Drug Act’ came into effect on 4th January 1983, considering as rare diseases or conditions those that affected fewer than 200,000 people in the USA, or – if the number was higher – it could not be expected that the costs of the production of effective drugs and their commercialisation in the USA could be covered through the sale of the drugs in the USA alone. The approval of orphan drug status gave the manufacturers tax reductions, allowances for clinical tests, accelerated approval through the FDA and the exclusive protection of sales rights for seven years, during which no other company was allowed to launch the same compound.

In 2006, the European drug regulatory agency, EMEA, granted the liver cell therapy orphan drug status recognising it as a pharmaceutical for rare diseases. (Figure: Cytonet)
The exclusive sales rights were massively criticised. This is the most attractive aspect of an orphan drug, because it gives the manufacturer the exclusive right to sell a particular product for seven years. For patients and health insurance companies, exclusive sales rights could equate to unreasonably high prices. The term ‘the same’ compound has also frequently been a matter of legal dispute. However, the Orphan Drug Act can be seen as a big success. Within the first ten years of its introduction, 642 compounds were given orphan drug status, and 136 were eventually approved as drugs. The majority of these products, in particular those produced with biotechnological methods, were developed at universities and hospitals as well as at small- and medium-sized companies. The Orphan Drug Act was an important growth factor for the American biotech industry.

Latecomer Europe

However, it took quite a long time before other countries introduced similar legislation to tie in with the American experience and success. In 1993, Japan was the second country to put an Orphan Drug Law into effect, and six years later – eagerly awaited by patients and associated organisations – the European Union launched the ‘Directive on Medicinal Products for Rare Diseases’, which came into force in April 2000. The European drug regulatory authority, EMEA, set up a Committee for Orphan Medicinal Products (COMP) that reviews applications from persons or companies seeking orphan drug designation. It is the first EU committee to have patient organisations as full members on its board. Furthermore, the COMP vice-chairman is a representative of patient organisations.
Cancer vaccines of immatics are already in clinical development. (Photo: immatics)
The incentives created by the European legislation for companies to develop orphan drugs were based on the American experience. EMEA offers advice and support in the optimisation of the development and preparation of the dossier according to the regulatory requirements. The approval procedure is accelerated and simplified through direct admission to the centralised process of the EMEA. In addition, the fees for the proposal, approval and examinations are either reduced or waived. However, the most attractive stimulus for seeking orphan drug designation is the developers’ exclusive right to sell the orphan drug for the approved indication for a period of ten years.

The ‘orphan disease’ criteria differ slightly in the USA, Japan and Europe: In Europe, orphan medicinal product designation is given to products intended for diseases that affect no more than 5 people in 10,000; in the USA, it is given to products for diseases that affect no more than 7.5 people in 10,000 and in Japan no more than 4 in 10,000. Orphan drug status is granted on the condition that no effective therapy is available in the specific indication applied for.

An important simplification for developers is the decision announced by the FDA and EMEA at the end of 2007, which provided for the use of the same application forms when seeking orphan drug designation in the USA and the EU. This means that format and content are harmonised in the USA and the Europe, thereby considerably accelerating parallel application and labelling. However, the two agencies still review the applications independently from one another.

Orphan Drug Directive had a huge response in Europe

The Orphan Drug Directive had a huge response in Europe. 320 applications were submitted up to the end of 2003 (32 months after the directive became effective) alone. According to information from the Association of Research-based Pharmaceutical Companies, 47 drugs have been approved as orphan drugs in the EU. The majority of these 47 are already known drugs from big pharmaceutical companies that already own the commercialisation right and who have applied for orphan drug designation in new, rare indications. Novartis’s Glivec for the treatment of acute lymphatic leukaemia or chronic myeloid leukaemia is one such example.

There are hardly any true innovations among the orphan drugs approved up until now; but there are many innovative drugs among the applications submitted by mainly small- and medium-sized companies. For many new biotechnology company drug developments, the COMP recommendation for the conferral of orphan drug designation is of central importance and it is expected that these innovative drugs will be approved for the treatment of rare diseases within the next few years. The European Directive on Medicinal Products for Rare Diseases would then, as was the case in the USA a few years ago, become an innovation driver for medical and pharmaceutical biotechnology in Europe and fulfil its true purpose, namely to give patients with severe, previously incurable diseases hope of effective future therapies.

The focus this month is on orphan drugs and a number of articles will present new drug developments by biotech companies and research institutions in Baden-Württemberg designed to combat rare diseases.

EJ – 29 August 2008
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Website address: https://www.gesundheitsindustrie-bw.de/en/article/dossier/orphan-drugs-medicine-for-the-treatment-of-severe-diseases