22 December 2005 print
Task Force Update
Spotlight on...
EU Policy
National Policy News
Research in Action
Orphan Drugs
Patients Associations
Press & Publications
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A new editor for OrphaNews Europe
Unfortunately for the Rare Diseases Task Force, Sally Goodman, who was assisting in running its secretariat and editing its newsletter, is leaving for a newly created position at the French national cancer institute. She was so good and so dedicated that it is hard to accept her departure. The good news is that she will be replaced by Louise Taylor who is already an experienced editor in the scientific sector. Thank you so much Sally and good luck ! Welcome Louise !

May we also take this opportunity to thank you for your support and collaboration during 2005 and to wish you all a very happy festive season.

Happy New Year 2006

Deadline for submissions

We welcome your contributions to OrphaNews Europe.
Please send your ideas for articles by contacting the editor here.

The next edition will appear in mid-January.
Deadline for the next edition is
6 January 2006.


Task Force Update
Report from the 4th Meeting of the Rare Diseases Task Force
The fourth meeting of the RDTF took place in Luxembourg on 14 December. The activities of the past year were reviewed and plans for next year discussed. The establishment of OrphaNews Europe seems to have been welcomed by the rare diseases Community as the newsletter already has over 6,500 readers. A suggestion was made to do a survey to investigate the profile of these readers.

The European Conference on Rare Diseases organised in Luxembourg by Eurordis in June 2005 was also a major achievement of the year. The conference gathered 320 participants, half of them being patient representatives. It was suggested that more resources be attributed for funding fellowships at the next conference to be held in Lisbon in October 2007, in order to promote participation from central and eastern Europe.

The working group on classification and coding will hold its first meeting in mid-2006. A preliminary meeting with WHO to discuss the revision of the International Classification of rare diseases took place in Geneva on 21 December. The working group on health indicators will meet for the first time on 30 January in Paris. It will focus on the identification of indicators which might help in comparing outcomes for patients in the different European countries. A feasibility study of using death certificates for that purpose is also planned. The working group on standards of care had two meetings this year. It issued a report and accompanying annexes on European centres of reference published at the end of September. As this report is considered to be very strategic, the RDTF decided to continue working on this issue, to gather more information on the current situation in the 25 member states and to have a more in-depth analysis of the consequences of the different models of organisation as currently established in Europe. A meeting of this working group will take place in Luxembourg in September 2006.

The DG Sanco draft work programme and call for proposal was presented. It should be published in January 2006 and applications will be expected for April. The EU Health portal was also presented. A section will direct citizens towards the national and EU sources of information on rare diseases. Many other subjects were also presented and discussed. The complete report of the RDTF meeting will be available as soon as the minutes are officially approved.


Spotlight on...
...ERDITI: encouraging new rare disease therapies through public-private partnership
A new form of partnership between academic institutions and pharmaceutical companies, the European Rare Diseases Therapeutic Initiative (ERDITI), is encouraging the development of treatments for rare diseases by reviving interest in compounds that have been ‘left on the shelf’ and looking at alternative uses for those currently in development.

ERDITI was set up in 2004 under the sponsorship of the European Science Foundation and is coordinated by the French Institute for Rare Diseases Research in Paris. The ERDITI partnership is based on a charter which defines a streamlined facilitated process of collaboration between academic teams and pharmaceutical companies to develop drugs for rare diseases. The charter comprises three parts : a working procedure, a standard material transfer agreement and a standard intellectual property rights agreement.

Despite five years of European orphan drug regulation (and similar legislation in the USA, Japan, Australia and Singapore) to promote development of therapies for rare diseases, many pharmaceutical companies are not prepared to commit to the costs involved in the compound screening and preclinical development necessary to develop a drug for the extremely limited markets represented by rare disease patients. However, these same companies have a potential treasure trove of compounds developed for more common diseases but that were abandoned or failed to achieve registration. The principle behind ERDITI is to open up this treasure trove to academic researchers interested in developing the compounds into a potential therapy for a specific rare disease. “The availability of such compounds could allow us to shortcut the traditional route of pharmaceutical development and evaluate swiftly and at minimal costs drug candidates for the treatment of rare diseases”, says Claire Roussel, ERDITI’s coordinator.

The heterogeneity of rare diseases and their sheer number – over 7000 identified to date – means that most are poorly characterised and lack diagnostic tools and appropriate treatment. Through the ERDITI partnership, researchers working on the characterisation of a particular rare disease present a proposal for evaluating a compound’s potential therapeutic interest through in vitro and animal models to ERDITI’s scientific advisory board. The board, made up of experts from both the public and private sectors, assesses the proposal, and, if accepted the ERDITI coordinators then consult with the pharmaceutical partners on the availability of the selected compounds.

“The industry partners involved in the ERDITI project are convinced of the usefulness of such a partnership. But for each given proposal, the scientific committee must be assured of the pertinence of the scientific hypothesis, that the study will be well run and of quality and that it will answer the question being asked” says Anne Bousseau, the Sanofi-Aventis representative on ERDITI’s scientific board.

If a suitable compound is identified in a drug company’s compound library they sign an agreement with the academic team in which they agree to provide ‘reasonable quantities’ of the drug for preclinical studies. The company has no obligation to produce further quantities of the compound but it must allow the academic team to synthesise the compound as required for the research.

The academic team, in turn, agrees to share its research data with the drug company. The results applicable to rare diseases remain the sole property of the academic partner in terms of publication and patent application. Any results that have applications outside rare diseases become the property of the drug company.

At this point the company can decide to exploit the results of the preclinical studies in which case it negotiates a licence agreement with the research team. Alternatively it may decide not to continue development of the compound into a potential orphan drug in which case it grants licence rights for the development of the compound by a third party.

So far four major drug companies - Sanofi-Aventis, GlaxoSmithKline, Roche, and Servier – and ten European academic institutions are partners in ERDITI but researchers from any European research institute can apply. The coordinators plan to open ERDITI to other pharmaceutical companies or biotechnology societies as soon as they have shown that ERDITI is a feasible initiative. ‘The ERDITI project has been developed at an optimal moment for researchers as the potential of recent advances in human genomics and pathophysiological knowledge of rare diseases now open the way to therapy development’, says Pascale Borensztein, general secretary of the French Institute of rare disease research. ‘We hope that more researchers will see the potential of this partnership approach in the future’, she adds.

One of the future challenges for ERDITI is funding. No direct funding is provided to researchers, and pharmaceutical partners are not obliged to fund either development or clinical trials. The European researchers interested in establishing an ERDITI partnership must currently find funding for their projects from the usual sources of academic financing. However, the coordinators remain optimistic that companies will be interested in investing because of the incentives provided by orphan drug regulation once their compound has been designated. In the future they hope that new forms of financing can be envisaged on a European scale to support the development of these new drugs.

For further information contact the ERDITI coordinator: Claire Roussel


EU Policy News
DG Research
On-line access to EC-funded rare disease projects
A list of projects concerning rare diseases that have been funded under the EC’s Sixth Framework programme is now accessible on the CORDIS website. The projects featured include those funded under the themes of major diseases, fundamental genomics and biotechnology, as well as those under horizontal actions, research for policy support and the ERA-Net networking programme.
DG Enterprise
New proposal on advanced therapies
Following a stakeholder consultation exercise, the European Commission’s DG Enterprise put forward a proposal last month for new EU wide rules to facilitate gene, cell and tissue-based therapies. These advanced therapies bring exciting new treatment opportunities for patients allowing, for example, diseased tissue to be replaced with bioengineered products.

With this proposal the Commission covers all advanced therapies within a single, integrated and tailored European regulatory framework. The current lack of an EU-wide framework has led to divergent national approaches as to the legal classification and authorisation of advanced therapy products. The main elements of the Commission proposal are a centralised marketing authorisation procedure, to benefit from the pooling of expertise at European level and direct access to the EU market; a new and multidisciplinary expert Committee (the Committee for Advanced Therapies), within the European Medicines Agency (EMEA), to assess advanced therapy products and follow scientific developments in the field; tailor-made technical requirements, which are adapted to the particular characteristics of these products; strengthened requirements for risk management and traceability; a system of low-cost, top-quality scientific advice provided by EMEA; and special incentives for small and medium-sized enterprises. Ethical decisions about the use or non-use of germ cells or embryonic stem cells remain under the full responsibility of individual Member States.

The Commission proposal will now be forwarded to the European Parliament and Council for co-decision.

Patient groups, and in particular Eurodis, the European Organisation for Rare Diseases, have been closely involved with the preparation of the proposal from the beginning. Eurordis recently made a presentation to an industry hearing on the topic to present their patient representatives' views on the subject. A position paper will soon be published on the Eurordis website .

Support for SME innovative drug development
The European Medicines Agency has launched an SME Office to provide administrative and procedural assistance to small and medium-sized enterprises (SMEs) seeking to develop and market new medicines. The launch follows the adoption of a new Commission Regulation aimed at promoting innovation and the development of new medicinal products by SMEs. The Regulation (2049/2005), which lays down special financial and administrative provisions for SMEs, was adopted on 15 December 2005. Once the Regulation comes into effect, SME companies that are developing medicinal products for human or veterinary use will be able to benefit from a number of incentives, including administrative and procedural assistance and fee reductions for scientific advice.

The EMEA has also announced new rules on fees for registration of medicines based upon a proposal from the European Commission. A number of fees will be reduced, reinforcing the principle of proportionality between the fees levels and the services provided by the Agency. The new regulation puts the fees system in line with the new pharmaceutical legislation in the EU and the new responsibilities conferred to the EMEA.


National & International Policy Developments
Policy developments in EU member states
UK MP calls for public debate on first cousin marriages
A British Labour MP, Ann Cryer, has called for a public debate on the genetic risks of marriages between first cousins in Britain's Pakistani community after reports of an unusually high rate of autosomal recessive disorders among children near her constituency in Bradford, in northern England. She made her comments in an interview with the BBC.

In the interview Ms Cryer described the risk of genetic disorders in children of first cousin marriages as a public health issue, arguing that British Asians should “look outside the family for husbands and wives for their young people." In Bradford, it is estimated that more than three quarters of all British Pakistani marriages are between first cousins.

In an unpublished study from 2002, John Benson, a consultant paediatrician at the Queens Park Hospital Blackburn found that the Asian population in the Bradford area has a 12 fold increased risk of recessive disorders compared to the white population with 13 new recessive disorders per 1000 births. Responding to Ann Cryer’s comments in the BMJ he advises that 'the simple message for the Asian community who favour cousin marriage is that, if a recessive disorder is found in the family it is vital to seek genetic advice before marrying and having children'.

50 million pound boost for UK stem cell research
The UK government has agreed to provide additional funding of £50 million for the development of the country’s stem cell research effort. The decision comes in response to recommendations from the UK Stem Cell Initiative (UKSCI) set up by the government in March as an independent advisory body to develop a ten-year research and development strategy on stem cells, with the aim of making the UK the most scientifically and commercially productive location for this activity over the coming decade.

The UKSCI report, published on 1 December 2005, provides a ‘road map’ for translating basic research in stem cells into new therapies to benefit patients. It gives an overview of the status of stem cell research in the UK and overseas and indicative costs for a strategy to maintain the UK’s position as a leader in basic research. The report recommends that the Government provide increased funding over the ten years to 2016 and set up public/ private partnerships to coordinate and develop stem cell research and technology. It argues the need for a consortium of pharmaceutical, healthcare and biotechnology companies backed by the Government to develop stem cell technology as a basis for new medical treatments and for a public/private partnership involving the Government and the UK Stem Cell Foundation to coordinate investment in research via the Research Councils and private finance. It also recommends strengthening the infrastructure supporting UK stem cell research via the consolidation of the UK Stem Cell Bank and the establishment of Centres of Excellence.

In a statement made in reply to the report, the UK government announced that it accepts these UKSCI recommendations in full, including the support of translational stem cell research and clinical trials, ensuring flexibility of stem cell research regulations and providing a platform for a sustained programme of public dialogue on stem cell research over the next decade. As a result of taking these recommendations forward total public sector funding for stem cell research will increase over the two year period 2006-8 to £100 million, representing additional investment of around £50 million.

Report from joint Italian/US meeting on rare diseases and orphan drugs
On 18 November, 2005 the Italian National Centre for Rare Diseases organised the international meeting “Rare Diseases and Orphan Drugs” at the Istituto Superiore di Sanità (Rome, Italy). The scope of the meeting was to give an overview of issues relevant to rare diseases and orphan drugs, from different public health as well as sociological standpoints. The meeting took place after the start of the bilateral Italy-USA agreement on joint research and development actions on public health problems, including rare diseases; thus the experience of the US NIH Office for Rare Diseases and topics concerning experiences on rare diseases and orphan drug regulations both at USA and European level were presented.

Recent initiatives of the Italian Drug Agency were illustrated such as a specific call for national projects on orphan drugs and the creation of the Italian Orphan Drug Registry at the Istituto Superiore di Sanità. Specific attention was given to Italian institutional activities undertaken to implement the National Network for Rare Diseases. Italy is implementing a new administrative asset, with a marked increase of autonomy for the regional governments on most topics, including health policies. It is thus highly relevant to discuss the new developments concerning those problems, including rare diseases, that require a strong co-ordination of initiatives. The meeting successfully contributed to an open discussion among major stakeholders, including policy makers, national (Ministry of Health) and regional bodies of the health system as well as many associations of people affected by rare diseases and their families.


Research in Action
New diseases & syndromes
New syndromes published on PubMed in November/December 2005
A Homozygous Mutation in the Lamin A/C Gene associated with a Novel Syndrome of Arthropathy, Tendinous Calcinosis and Progeroid Features
J Clin Endocrinol Metab ; Epub ahead of print ; 8 November 2005
New genes
New rare disease genes published on PubMed in November 2005
Identification of a recurrent breakpoint within the SHANK3 gene in the 22q13.3 deletion syndrome
To read more about "Deletion 22q13"

J Med Genet. ; Epub ahead of print ; 11 November 2005
Mutations in the beta-subunit of the epithelial Na+ channel in patients with a cystic fibrosis-like syndrome
To read more about "Cystic fibrosis"

Hum Mol Genet. ; 14(22):3493-8 ; 15 November 2005
New clinical research
New clinical trials and research on Orphanet
An open-label, single centre phase I/IIa dose titration study of ACZ885 (human anti IL-1beta monoclonal antibody) to assess the clinical efficacy, safety, pharmacokinetics and pharmacodynamics in patients with NALP3 mutations

A single centre trial

POET: Prevention of endometrial tumours: randomised trial of the intrauterine system MIRENA containing progestogen to reduce endometrial hyperplasia and cancer in women with HNPCC

An international multi-centre trial

To register your interest in participating in a clinical trial visit Orphanet.

Extensive scanning of the calpain-3 gene broadens the spectrum of LGMD2A phenotypes
To read more about "Calpainopathy"

J Med Genet. ; 42(9):686-93 ; September 2005
New clinical research published on PubMed in November/December 2005
Novel adopted immunotherapy for mixed chimerism after unrelated cord blood transplantation in Omenn syndrome
To read more about "Omenn syndrome"

Eur J Haematol. ; 75(5):441-4 ; November 2005
New therapies for sickle cell disease
To read more about "Sickle cell anemia"

Hematol Oncol Clin North Am. ; 19(5):975-87, ix ; October 2005
Sildenafil citrate therapy for pulmonary arterial hypertension
To read more about "Pulmonary arterial hypertension"

N Engl J Med. ; 353(20):2148-57 ; 17 November 2005
New therapeutic & diagnostic approaches
New therapeutic & diagnostic approaches published on PubMed in November/December 2005
Excess non-spine fractures in women over 50 years with celiac disease: a cross-sectional, questionnaire-based study
To read more about "Celiac disease"

Osteoporos Int ; 16(9):1150-5 ; September 2005
Asymptomatic inflammatory bowel disease presenting with mucocutaneous findings
To read more about "Crohn disease"
To read more about "Ulcerative colitis"

Pediatrics ; 116(3):e439-44 ; September 2005
Prevention of colorectal cancer by colonoscopic surveillance in individuals with a family history of colorectal cancer: 16 year, prospective, follow-up study
To read more about "Colon cancer, familial nonpolyposis"

BMJ ; 331(7524):1047 ; 5 November 2005
Obesity is an independent contributor to functional capacity and inflammation in systemic lupus erythematosus
To read more about "Lupus erythematosus"

Arthritis Rheum. ; 52(11):3651-9 ; November 2005
Home treatment for Fabry disease: practice guidelines based on 3 years experience in The Netherlands
To read more about "Fabry disease"

Nephrol Dial Transplant. ; Epub ahead of print ; 25 October 2005
Iatrogenic harm caused by diagnostic errors in fibrodysplasia ossificans progressiva
To read more about "Fibrodysplasia ossificans progressiva"

Pediatrics ; 116(5):e654-61 ; November 2005
Genetic testing
New research on genetic testing published on PubMed in November/December 2005
Assessment of the genetic causes of recessive childhood non-syndromic deafness in the UK - implications for genetic testing
To read more about "Deafness, autosomal recessive, nonsyndromic, sensorineural, type DFNB"
To read more about "Connexin 26 anomaly"

Clin Genet. ; 68(6):506-12 ; December 2005

Orphan Drugs
New designations & authorisations in Europe
EMEA orphan drug decisions
At its meeting on 7 December 2005, the EMEA’s Committee for Orphan Medicinal Products (COMP) adopted 5 positive opinions on orphan designation for medicinal products:
  • E. Coli heat-shock protein 70 with bovine retinal S-antigen for treatment of autoimmune uveitis
  • Human monoclonal antibody against HLA-DR for treatment of chronic lymphocytic leukaemia
  • Purified inactivated Japanese encephalitis SA14-4-2 virus vaccine for prevention of Japanese encephalitis
  • Lentiviral vector containing the human Wiskott Aldrich syndrome protein gene for treatment of Wiskott Aldrich syndrome
  • Vandetanib for treatment of medullary thyroid carcinoma

  • EMEA COMP opinions in December 2005

    On 28 October, the Committee on Human Medicinal Products granted marketing authorisation to Revatio (sildenafil citrate) for the treatment of patients with pulmonary arterial hypertension. This is the same molecule used in Viagra for erectile dysfunction. It brings to 22 the number of orphan drugs with marketing authorisation in the EU.

    EMEA CHMP decisions in October 2005

    Details of all orphan designations and authorisations granted to date by the European Commission are entered in the Community Register of Orphan Medicinal Products

    New designations & authorisations in USA
    FDA approves thalidomide for multiple myeloma
    Last month, the US Food and Drug Agency issued an 'approvable letter' in response to Celgene’s request for marketing authorisation for thalidomide in the treatment of multiple myeloma. However, the Agency has requested revised product labelling with the specific indication of newly diagnosed multiple myeloma and updated safety information, as well as some additional patient information before taking a final decision.

    Thalidomide has already received orphan drug designation in Europe and Japan for the same indication.


    News from the Patients Associations
    Eurordis update
    Rare Diseases as a Public Health Priority: Eurordis clarifies the issue
    In November 2005, Eurordis adopted a founding text entitled 'Rare Diseases: understanding this Public Health Priority' to clarify the concept of rare diseases and their interaction with public health policy. The text is a unique document covering all aspects of rare diseases: definition of the concepts involved; characteristics and specificities of rare diseases; figures; description of the social, medical and financial impact of rare diseases on the lives of patients and their families; need for raising public awareness; need for appropriate funding and for appropriate health systems and professional care; and, last but not least, the absolute necessity to empower patients to break their isolation.

    The paper was written by Eurordis with input from information gathered at the European Conference on Rare Diseases in Luxembourg in June 2005. Eurordis members and others in the rare diseases community were directly consulted in the process and had many opportunities to contribute to the document and give their feedback before the final adoption of the document took place in November 2005. Eurordis is now encouraging the wide dissemination of this document to ensure that it achieves its aims and is used extensively.

    A new community for patients: the Prader-Willi mailing list
    Thanks to a new initiative from Eurordis people living with Prader-Willi in the EU now have the opportunity to be part of a new patient community.

    The community is a virtual discussion group and uses a monitored online mailing list. Patients are able to exchange information, messages, or simply chat with other people who have the same issues. This virtual community should be of special interest to isolated patients and carers. If you are interested in participating in the list, please visit the Eurordis medical list site. Similar lists for Ichthyosis, Xeroderma pigmentosum and Guenther's Porphyria will start soon.

    If you wish to create a list for your particular disease, please contact Eurordis


    Press & Publications
    New books
    Prenatal tests – the facts
    Authors: L De Crespigny, FA Chervenak
    Published by Oxford University Press, September 2005

    Atlas of Metabolic Diseases – 2nd edition
    Authors: WL Nyhan, BA Barshop, PT Ozand
    Published by Hodder Arnold, September 2005

    Oxford Desk Reference – Clinical Genetics
    Authors: HV Firth, JA Hurst, JG Hall
    Published by Oxford University Press, July 2005

    Medical Genetics
    Author: Ian D Young
    Published by Oxford University Press, June 2005

    Management of Prader-Willi Syndrome
    Authors: : Merlin Butler, Phillip D.K. Lee, Barbara Y. Whitman
    Published by Springer-Verlag, New York, December 2005.


    What's on where?
    In January
    10th International Conference on thalassaemia and haemoglobinopathies
    This meeting, held in conjunction with the 12th International TIF meeting for thalassaemia patients and parents, will cover all aspects of thalassaemia and haemoglobinopathies from molecular genetics to prevention strategies to clinical care. The patients meeting will focus on current and future therapeutic approaches and on possible complications of the disease.

    Date: 7 – 10 January 2006
    Venue: Dubai, United Arab Emirates

    Phacilitate Cell & Gene Therapy Forum 2006
    This conference will address the latest regulatory challenges for cell and gene therapies in North America and Europe and the state of the art in research in the field.

    Date: 30 January – 1 February 2006
    Venue: Baltimore, USA

    In February
    International Symposium on Human Genomics and Public Health
    Held in association with the XXXI Annual Conference of the Indian Society of Human Genetics, this event will address different ways in which a human genomics approach can be used to help understanding in system biology and to address public health concerns.

    Date : 27 February-01 March, 2006
    Venue: New Delhi, India

    In March
    18th Annual Drug Information Association Euromeeting
    The 2006 Programme will address the challenges of the revised Pharmaceutical Legislation, which is the driving force for review of all aspects of regulatory achievement and will provide an opportunity to discuss the latest developments in important European initiatives, including paediatrics, advanced therapies, the technology platform, pharmacogenomics, pharmacovigilance and risk management planning.

    Date: 6-8 March 2006
    Venue: Paris, France

    International Plasma Protein Congress (IPPC)
    The programme will provide updates and perspectives on the latest issues affecting and changing the plasma protein therapeutics industry, as well as on future developments.

    Date: 7-8 March 2006
    Venue: Prague, Czech Republic

    In May
    1st International Education Conference on Batten Disease
    Leading researchers and practitioners from all around the world working in the field of Batten Disease (also called juvenile neural ceroid lipofuscinos or Spielmeyer-Vogt Disease) will present the state of the art and discuss critical issues related to people with Batten disease

    Date: 3-6 May 2006
    Venue: Örebro, Sweden


    Orphanews Europe, the newsletter of the Rare Diseases Task Force
    Orphanews Europe is supported by the European Commission's DG SANCO
    and the French Muscular Dystrophy Association (AFM)
    Editor-in-chief: Dr Ségolène Aymé
    Editor: Sally Goodman
    Contact Us
    Editorial Board: Ségolène Aymé, Catherine Berens, Helen Dolk, Anders Fasth, Muriel Herasse,Edmund Jessop, Jordi Llinares-Garcia, Jérôme Parisse-Brassens, Helmut Popper, Elena Prats, John Ryan, Janos Sandor, Arrigo Schieppati, Rumen Stefanov, Domenica Taruscio, Joan Luis Vives Corrons
    For more information on the Rare Diseases Task Force
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