The fourth meeting of the Rare Diseases Task Force will take place in Luxembourg on 14 December 2005.
Members of the Task Force will discuss the future work programmes of the three working groups - on standards of healthcare, on public health indicators and on coding and classification for rare diseases - and on future funding opportunities for European rare disease research.
Meeting agenda
The second RDTF working group, dedicated to Public Health Indicators for rare diseases, will meet for the first time on 30 January 2006, in Paris. This working group of European experts is being led by Juliette Bloch of the French national institute for public health surveillance (InVS). Members of the group will discuss the selection of rare diseases with high priority for epidemiological surveillance. The group will also determine the definition of rare diseases which can be identified in mortality certificates and develop a European-level feasibility study for using mortality data as public heath indicators.
The US Orphan Drug Act (ODA) was passed in 1983 with the aim of stimulating the development of drugs for rare diseases, defined as those affecting fewer than 200,000 people in the United States. The law provides 7-year marketing exclusivity to sponsors of approved orphan products and a tax credit of 50 percent of the cost of conducting human clinical testing. Exclusive marketing rights begin on the date that the marketing application is approved by FDA for the designated orphan drug, and applies only to the indication for which the drug has been designated and approved. Other companies must prove clinical superiority before they are allowed to market another version of the same drug. Since 1997, companies developing orphan products also benefit from an exemption from the usual user fees charged by the Food and Drug Administration (FDA). Applications for orphan drug designation are handled by the Office for Orphan Product Development (OOPD), part of the FDA.
The OOPD also provides research grants for phase 1, 2, or 3 clinical testing of new therapies to treat orphan diseases prior to approval. In financial year 2006, over 14 million dollars will be made available for this programme. So far 39 orphan products have been granted marketing approval following funding of clinical studies through the scheme.
The US ODA in figures:
Since 1983:
Marlene E Haffner, MD, MPH, has been director of the Office of Orphan Products Development (OOPD) at the U.S. Food and Drug Administration (FDA) since 1987, a responsibility she finds exciting, challenging and worthwhile. 'The work that I and my staff do everyday has a significant positive impact on the lives of people in the US and beyond', says Dr Haffner.
OrphaNews Europe asked her about the main lessons learnt from over 20 years of orphan drug legislation in the USA and the challenges still remaining:
OrphaNews Europe: Looking back over the last 22 years since the US Orphan Drug Act came into effect, what are the main learning points that you have taken on board from this experience?
MH: I guess the first thing that has been learned from the US Orphan Drug Act is that - IT WORKS! I have no idea what success the initial crafters of the programme envisioned, but to have 272 products serving 14 million in the US is a fantastic achievement. And as further testament to the success of the programme in the US, it has been adopted or imitated in Japan, Australia, the EU and beyond. But beyond the fact that the programme works, some of the other lessons learned include:
- Most orphan diseases are serious/life threatening diseases. Most are chronic. They are not treated within a week - 10 days worth of drugs and are forever better. This means that if a drug is given chronically, the sponsor has a greater chance to make a profit in time.
- Many (about 50%) of orphan diseases occur in children - our most vulnerable population.
- A large percentage of rare diseases are of genetic origin, 'personalised' pharmacogenetic drug development will find fertile ground in the study and treatment of rare diseases.
Read the full interview with Marlene Haffner
The German Research Foundation (DFG), the central research organisation promoting research at universities and other publicly financed research institutions in Germany, is to support a Priority Programme in gene therapy from the beginning of 2006.
The programme entitled 'Mechanisms of gene vector entry and persistence' will attempt to systematically investigate and improve the foundations of somatic gene therapy using state of the art methods. Gene vectors can deliver genes into cells undamaged and in a targeted way, making them an attractive tool for the treatment of hereditary diseases. Their benefits are undisputed, but their potential undesirable side effects remain largely unexplored. This international project, which is deliberately open-ended with regard to its findings, will focus on problems such as dosage, persistence and integration of gene vectors. It may also help to consolidate Germany's role as a location for gene therapy research. The DFG is contributing 10.5 million euros to the programme which will initially run for three years but may be continued for a further three years.
For further details contact the programme coordinator, Pr. Dr Christopher Baum, at the Paediatric Department of Haematology and Oncology of Hannover Medical School.
In June 2005, Ireland's new Disability Act passed into law. The new Act provides a statute-based right for people with disabilities to an assessment of disability-related health, personal social service and educational needs.
The new Act notably includes a section on genetic testing, requiring that consent of the person being tested is obtained before processing of any genetic data derived from the test and prohibiting the processing of genetic data in relation to employment of a person (except in certain circumstances), or the taking out of life insurance, health insurance or general insurance policies. In addition, the processing of genetic data is prohibited unless 'all reasonable steps have been taken to provide the data subject with all appropriate information concerning the purpose and possible outcomes of the proposed processing, and any potential implications for the health of the data subject which may become known as a result of the processing'. The law relating to genetic testing will come into effect on 31 December 2005.
http://www.oireachtas.ie/documents/bills28/acts/2005/a1405.pdf
The French Institute for Rare Diseases (GIS-Institut des Maladies Rares) has announced the results of its latest call for projects in rare disease research. 35 new research projects, targeting a wide range of rare diseases, will be jointly financed by the French National Research Agency (ANR) and the French Association for Muscular Dystrophy (AFM). The successful projects including both basic and applied research projects, were chosen out of a total of 160 proposals, after evaluation by the joint scientific committee of the Institute and the ANR, along with other external experts. The 35 projects will share a global budget of just over 11 million euros over a period of two to three years.
The Institute’s call for projects in rare diseases is one of the priority initiatives outlined in the French National Plan for Rare Diseases, launched in November 2004, to boost and support rare diseases research in France. Further calls for proposals are planned for next year.
The French National Plan for Rare Diseases, launched in November 2004 by the French Ministries of Health and of Research, has now been translated into Spanish. French, English, German and Italian versions are also available and can be accessed on the RDTF website. Please distribute the translated version of the Plan in your own language to your country's public health decision-makers and any other interested parties.
In an article in the November issue of Thorax, Dr Alex Jaffé argues that despite recent initiatives, the UK is failing to address the inequities in healthcare provision for children with rare lung disease. He reviews a number of successful initiatives and incentives for rare diseases in Europe, and beyond and concludes that in the UK there is an urgent need for a unified approach at a national level to address inequity and provide solutions for rare disease patients.
At its 33rd Session on 19 October 2005, the General Conference of UNESCO adopted the Universal Declaration on Bioethics and Human Rights.
The Declaration was drafted in response to the growing need to develop universally applicable ethical guidelines within a context of the cultural pluralism inherent in bioethics, particularly with the rise in international collaboration in scientific activities. It aims to establish the conformity of bioethics with international human rights law. The Declaration focuses strongly on the issue of informed consent and on equitable access to medical, scientific and technological developments.
UNESCO’s member states will not be bound by the Declaration. Instead it provides principles that may serve as contours for legislation, regulation, and policy decisions within the Member States but each country’s lawmakers are left to decide between different positions, guided by the principles expressed in the Declaration. It invites Member States to take appropriate measures, to encourage the establishment of ethics or bioethics committees, and to create processes for risk assessment.
Member States will, however, be required to provide reports every five years to the Director-General of UNESCO with the aim of disseminating information on the implementation of the principles contained in the Declaration: in terms of legislation, regulation, and jurisprudence, as well as in the decisions of national ethics or bioethics committees and other ethics or similar commissions. The Declaration will be examined after five years in the light of scientific and technological development and will, if necessary, be revised in accordance with UNESCO’s statutory procedures.
The US Food and Drug Administration has approved the first transplant of foetal stem cells to cure Batten disease (or infantile and late-infantile neuronal ceroid lipofuscinosis) a group of rare, fatal genetic disorders that affect the central nervous system of children.
The Phase I trial will be conducted by Stem Cells Inc., a company based in California. Affected children will receive injections of human neural stem cells into their brains with the hope that these cells will spread throughout the brain and produce both of the lysosomal enzymes missing in the subtypes of Batten disease being studied in the clinical trial. Children enrolled in the study will be evaluated with standardised measures of development, cognition, behaviour and language for one year following transplantation. Trial patients will also be asked to commit to a four-year follow-up study.
This is the first-ever FDA-approved clinical trial to use a purified composition of human neural stem cells as a potential therapeutic agent in humans. Stem Cells Inc. must now seek Institutional Review Board approval from the medical institutions where the trials will take place, including the Stanford University School of Medicine.
Nearly 300 different diseases and syndromes affecting the skin are known to be of genetic origin. The Geneskin project, launched in July 2005 and funded for three years under the European Commission’s Sixth Framework Programme (contract LSHM-CT-2005-512117) with over 1.2 million euros, was set up to coordinate and structure the dispersed expert knowledge linked to rare genetic skin diseases that currently exists across Europe by building a European Consortium of multidisciplinary experts in clinical and molecular diagnosis, management and innovative therapy...
...Read more about Geneskin
Mutations in dynamin 2 cause dominant centronuclear myopathy
Mutations in SEPT9 cause hereditary neuralgic amyotrophy
Sequence variants in SLITRK1 are associated with Tourette's syndrome
Severe expressive-language delay related to duplication of the Williams-Beuren locus
Stiff child syndrome with mutation of DYT1 gene
Congenital glutamine deficiency with glutamine synthetase mutations
Study of environmental, lifestyle, medical, family history, and genetic risk factors involved in amyotrophic lateral sclerosis in a homogeneous population (Quebec) and a diverse population (France)
An international multi-centre trial
Molecular epidemiology of Usher Syndrome in France
An international multi-centre trial
To register your interest in participating in a clinical trial visit Orphanet.
Aminoglycoside suppression of nonsense mutations in severe hemophilia
Caudate volumes in childhood predict symptom severity in adults with Tourette syndrome
At its meetings on 19 October and 9/10 November 2005, the EMEA's Committee for Orphan Medicinal Products (COMP) adopted 11 positive opinions on orphan designation for medicinal products for the following indications:
In October and November, the FDA's Office of Orphan Products Development granted orphan drug designation for medicinal products for the following indications:
In this BMJ article the authors argue that the cost effectiveness of orphan drugs should be treated in the same way as for other healthcare technologies in the context of the UK's National Health Service.
A second article in the BMJ describes how a national decision in the UK to provide therapies for a group of rare disorders prevented local funding for other vital services in the West Midlands region of the country.
In the November issue of the Eurordis newsletter, Fide Mirón, a young Spanish woman suffering from Günther’s disease, tells a moving story of her will to live and her battle for recognition.
Eurordis has recently published its position on the legitimacy and transparency of non governmental organisations (NGOs) calling for a better distinction between lobbying activities by stakeholders with a financial interest, and advocacy activities by groups of individuals or associations voicing citizens’ needs and views on critical issues such as health and human rights.
In a context where both clinicians and regulators are becoming more open-minded in their attitudes to alternative clinical trials methodology for the small populations represented by rare disease patients, the launch of two new journals devoted to clinical trials is a welcome development.
BioMed Central is to launch its journal Trials in January 2006. The new journal will be an open access, peer-reviewed, online-only journal which aims, according to its publishers, to experiment with, and then refine, innovative approaches to improving communication between trialists. It will consider manuscripts on any aspect of the design, performance, and findings of randomised controlled trials in any discipline related to health care, and will also encourage the publication of protocols, as well as commentaries and critiques on any aspect of a published trial”.
The Public Library of Science (PloS) will launch an international, peer-reviewed, open-access journal entitled PloS Clinical Trials in March 2006.
PloS Clinical Trials aims to broaden the scope of clinical trials reporting by publishing the results of randomised trials in humans from all medical and public health disciplines. Trials may investigate aspects of treatment or prevention, including drug or non-drug interventions. Non-drug studies may include (but not necessarily be restricted to) investigations of devices, surgical therapies, health service delivery, behavioural, lifestyle, psychological or educational interventions. Publication decisions will not be affected by the direction of results, size or perceived importance of the trial.
Submissions to both new journals are already being accepted.
Authors: T. Kazunari, K. Kazunori, N. Takuro
Published by Springer-Verlag; 30 November 2005
Authors: M. Artman, D. Woodrow Benson, D. Srivastava, M. Nakazawa
Published by Blckwell/Futura; 2005
Authors: M. A. Gatzoulis, L. Swan, J. Therrien, G. A. Pantely
Published by BMJ Publishing Group; 2005
The Centers for Disease Control and Prevention (CDC) of the US Office of Genomics and Disease Prevention has published its second report on genomics and population health.
Two chapters of the 2005 edition are of particular interest for rare diseases: Chapter 7 discusses recommendations for adding cystic fibrosis to the newborn screening panel in state public health programmes while Chapter 8 focuses on GeneTests, a publicly-funded information resource on genetic testing and its use in clinical practice which aims to enhance availability, access and quality of genetic testing for rare diseases.
Telethons are annual fund-raising events linked to marathon television shows which aim to raise both money for and the profile of rare and genetic diseases. Four European countries will be holding Telethons in December.
2-3 December, 2005: Telethon Belgium; Telethon France; Telethon Switzerland
16,17 and 18 December, 2005: Telethon Italy
A European conference organised by the European Federation of Neurological Associations focussing on what patients think about stem cell research and therapy.The Conference will be conducted as an open and interactive forum. 75% of the audience will be patients from Europe, whose conditions could be improved, or are already being improved, by stem cell therapies and treatments
Date: 15-16 December 2005
Venue: Brussels, Belgium
An international conference to explore the potential of genomics to improve the health of populations, its impact on society and the implications for specialists in public health and genetics.
Date: 26 January 2006
Venue: London, UK
A one day symposium on intersex conditions
Date: 1 May, 2006
Venue: Istanbul, Turkey
This conference will cover the latest developments in the fields of human genetics and genomics that are of interest to both clinicians and research scientists.
Date: May 6-9, 2006
Venue: Amsterdam, The Netherlands
The foremost meeting of the world human genetics community.
Date: 6-10 August, 2006
Venue: Brisbane, Australia