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Rare diseases: what’s next?
Rare diseases are life-threatening or chronically debilitating diseases with a prevalence lower than one per 2000 in the European Community or one per 1250 in the USA. Only a few of the 5000 recognised rare diseases have a prevalence close to those limits, and most of them are much rarer, such as muscular dystrophy, or haemophilia, and others are so uncommon that they are defi ned as being ultra-rare, such as Hutchinson-Gilford syndrome (progeria), or Whipple’s disease.
Rare diseases are also called health orphans—for most of them there is little knowledge of causes and eff ective therapies are limited. However, rare diseases are now included as priorities in public-health plans, and research-funding programmes in Europe and the USA are increasingly promoting basic and clinical research on these disorders. The five essays in today’s Lancet look at current activity in research into and treatment of rare diseases.(1-5)
As an example, in response to strong political engagement, French policy makers have implemented a series of measures to respond to the expectations of patients and their families. These measures include: the development of information for patients, health professionals and the general public; organisation of screening and access to diagnostic tests; and improvements to access to treatment and to the quality of health-care provision for patients.(6)
In Italy, a National Network Centres of Excellence for Rare Disease was established in 2001, and a National Registry of Rare Disease was launched by the Istituto Superiore di Sanità, the technical-scientifi c body of the national health system.(7)
The European Commission recently launched a public consultation on rare diseases, encouraging contribution from all member states about the development of national health policies to ensure equal access to and availability of prevention, diagnosis, treatment, and rehabilitation for people with rare diseases. The consultation was successful, with hundreds of comments from patients, families, scientists and institutions, and will form the basis for future proposals by the Commission. (8)
The USA was the fi rst country to establish legislation favouring the development of medicines to treat rare disease, the Orphan Drug Act, and a strong patients’ advocacy movement started more than two decades ago. Indeed, patients’ support groups are a leading force in the promotion of legislation that established incentives for the development of drugs for patients with rare diseases, and in general in bringing rare diseases to the attention of the public opinion. In today’s Essays, Segolené Aymé and colleagues4 discuss the role that patients’ advocacy groups for rare diseases had, and show how patients with rare diseases are now strongly supported by their advocacy groups, which are instrumental in determining policies and addressing unmet needs. Marlene Haffner and coauthors(2) review the history of and legislation for drugs to treat rare diseases and highlight the merits and limits of such laws.
Unfortunately, by contrast with the hopes that seemingly followed the legislation, the contribution of Europe to the approval of drugs for rare diseases has been meagre. In 6 years only 23 products have been approved for rare diseases, compared with 340 drugs for other diseases. For the rare diseases, an analysis of the documentation presented for the approval showed that for only nine of 18 drugs was there a randomised trial, and in general the ossiers often contained methodological limitations, such as inappropriate clinical design, lack of active comparator when available, and use of surrogate endpoints. (9)
The development of drugs for rare diseases has been concentrated in certain areas (particularly cancer and metabolic diseases), whereas no drugs have been approved for neurological diseases (a large number of which are rare) or for respiratory diseases. Furthermore the prices of such drugs are high, and hence they are a burden for health systems or patients. For instance, arsenic trioxide, an old product rediscovered as eff ective for second-line treatment of acute promyelocytic leukaemia, is still a very costly drug, at up to $50 000 for a full course. (10)
Imatinib for the treatment of chronic myeloid leukaemia (incidence one in about 60 000 people per year) and gastrointestinal stromal tumour (one in 62 500) uses, in Italy, about 10% of all hospital spending on anticancer agents; agalsidase beta, a drug for the treatment of Fabry’s disease, accounts for almost a fi fth of hospital spending on drugs for metabolic diseases. (11)
During the past decade signifi cant achievements have been made in research, drug development and public awareness of the social burden imposed by rare disease, but much remains to be done. Ultimately, the most relevant answers to patients’ needs will come from improved knowledge, in other words, from research. In this respect, Alain Fisher and colleagues (3) look at the successes and pitfalls of gene therapy, a potential approach to the treatment of rare genetic disorders.
Research requires adequate public funding because most drugs for rare diseases are not profi table for drug companies. Some basic research has been supported by an investment of €200 million as part of the European Union’s Sixth Framework Programme, although this sum is inadequate given that there are more than 5000 rare diseases. Hopefully the seventh Framework Programme will at least double this investment. Even then, the resources will not be suffi cient to cover drug development. Patients with rare diseases and their families have been waiting long enough. It is now time for action.
*Giuseppe Remuzzi, Silvio Garattini
Clinical Research Centre for Rare Diseases ‘Aldo e Cele Daccò’,
Mario Negri Institute for Pharmacological Research, Laboratori
Negri Bergamo, 24125 Bergamo, Italy
gremuzzi@marionegri.it
We worked closely with The Lancet’s editors on the topics and authorship of the essays, and we have helped to formulate Italian policy on rare diseases.
The Myelin Project wishes to thank Dr. Astrid James and the publishers of The Lancet for granting us permission to post this article.
References
1 Schieppati A, Henter J-I, Daina E, Aperia A. Why rare diseases are an important medical and social issue. Lancet 2008; 371: 2039–41.
2 Haffner ME, Torrent-Farnell J, Maher PD. Does orphan drug legislation really answer patients’ needs? Lancet 2008; 371: 2041–44.
3 Fischer A, Cavazzana-Calvo M. Gene therapy for inherited diseases. Lancet 2008; 371: 2044–47.
4 Aymé S, Kole A, Groft S. Empowerment of patients: lessons from the rare diseases community. Lancet 2008; 371: 2048–51.
5 Buckley BM. Clinical trials of orphan medicines. Lancet 2008; 371: 2051–55.
6 French National Plan for Rare Diseases 2005–2008. Ensuring equity in the access to diagnosis, treatment and provision of care. Nov 20, 2004. http://www.eurordis.org/IMG/pdf/EN_french_rare_disease_plan.pdf (accessed Dec 6, 2007).
7 Taruscio D, Ido MS, Daina E, Schieppati A. Tackling the problem of rare diseases in public health: the Italian approach. Community Genet 2003; 6: 123–24.
8 European Commission. Public consultation regarding a European action in the field of rare diseases. 2007. http://ec.europa.eu/health/ph_threats/non_com/cons_rare_dis_en.htm (accessed Jan 18, 2008).
9 Joppi R, Bertele V, Garattini S. Orphan drug development is progressing too slowly. Br J Clin Pharmacol 2006; 61: 355–60.
10 Cyranoski D. Arsenic patent keeps drug for rare cancer out of reach of many. Nat Med 2007; 13: 1005.
11 Osservatorio Nazionale sull’Impiego dei Farmaci. L’uso dei farmaci in Italia. 2006. http://www.agenziafarmaco.it/wscs_render_attachment_by_id/
11.272708.118250656748298dd.pdf?id=111.251385.1182344815039
(accessed on Jan 18, 2008).
See Editorial page 1972
See Essay Focus page 2039
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