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The 25th anniversary of the US Orphan Drug Act: an occasion to review achievements and consider future directions

A conference and a gala celebration were held in Washington, DC, on 19-20 May in order to commemorate the twenty-fifth anniversary of the Orphan Drug Act. The National Organization for Rare Disorders (NORD) was simultaneously celebrating 25 years of non-profit service for rare disease patients and their families. NORD, established in 1983 by rare disease patient group representatives and individuals, provided the advocacy behind the US Orphan Dug Act. The first such legislation in the world, versions of this vital regulation have since been adopted in other countries and continents around the world, including Australia, the European Union, Japan, South Korea and Taiwan.

The anniversary of the Orphan Drug Act was marked by a conference co-sponsored by the Food and Drug Administration (FDA) and the Drug Information Association (DIA), which took stock of the past 25 years of orphan drug legislation and considered future perspectives. Intended for researchers, biopharmaceutical representatives, patient groups, policy makers and clinical trial decision makers, the day-long event sought to identify the challenges and obstacles encountered in rare disease trials, and consider how to best optimise the orphan drug act provisions to bring rare disease drugs to market. An array of sessions considered the role of the orphan drug act, industry and patient perspectives, cooperation between the FDA and EMEA, the orphan product grants program, clinical trial regulatory monitoring, trial design for small patient populations, orphan drug application contents, and interactions with FDA review divisions.

A particularly interesting presentation was made by NORD founder and former president Abbey Meyers, who delineated the history of the Orphan Drug Act. In the 1970s, prior to passage of the legislation, the FDA created two task forces to study the issue of creating medicinal products with inherently low commercial value. At the time, Abbey Meyers was a housewife from Connecticut whose son was taking an experimental treatment that became unavailable. Trying to find a solution, she began contacting other patient organisations to see if they had experienced similar problems. This became the genesis for a coalition of patient organisations that eventually grew into NORD. With an actor from a popular television show bringing additional attention to the issue, the first legislation was created. This first bill proposed establishing a pool of government money from which companies could borrow for orphan drug development. If the product was approved, the company would pay the money back to the pool, along with any profits earned from sales. Both industry and congress soundly rejected this scheme. Meanwhile, the results of the task forces showed that pharmaceutical companies would be interested in rare disease products if there was a potential for profit, and at the very least the means to avoid losing money. The task forces recommended regulation that contained incentives such as exclusivity, tax credits, and protocol assistance. These recommendations, coupled with the lobbying of the burgeoning patient group coalition, led to the development of the Orphan Drug Act, which was signed into law in 1983.

Most of the original elements of the regulation are still intact today, despite several amendments over the years. In 1985, the definition of "orphan drugs" was broadened to include biologics. In addition, after heavy debate, the term rare disease was officially defined as a condition affecting less than 200,000 persons in the USA. In 1987, congress tried unsuccessfully to amend the bill to allow for "shared exclusivity" for two companies developing the same product for the same indication. In 1992, an amendment was proposed that would extend market exclusivity to nine years. This amendment would also impose a 120 million dollar sales ceiling for any given orphan drug product. Once reached, a competing product would be eligible for approval. Although passed by congress, this amendment was ultimately vetoed by then-president George Bush. Summing up the lessons gleaned from the past 25 years of the Orphan Drug Act, Abbey Meyers pointed out that the major controversies have occurred around the big money-making products, and were often sparked by those competitors that lost the race to marketing approval. Proposed changes have often favoured one corporation or one product. Abbey Meyers sums up the greatest achievement of NORD as their role in protecting the Orphan Drug Act from changes that would ultimately diminish its force.

Other notable presentations included an assessment of the accomplishments of the Orphan Drug Act from former Office of Orphan Products Development director Marlene Haffner, and a consideration of future challenges from Office of Rare Diseases director Stephen Groft. An exciting feature of the day was the unveiling of the Undiagnosed Diseases Program, a National Institutes of Health clinical research initiative specifically designed for medical cases that elude diagnosis. Read more about the Undiagnosed Diseases Program (below)

The next day it was NORD’s turn to blow out the candles. A gala dinner in the evening featured a speech by incoming NORD president and CEO Peter Saltonstall, as well as remarks by NORD board members Nancy Harris and Carolyn Asbury, and comments by the US Social Security Administration commissioner Michael Astrue. Attendees watched a video commemorating 25 years of orphan drug success, and were entertained by the Children’s Hospital Jazz Band.

Going forward, it is important to emphasise ways in which the international community can continue to share expertise and perspectives in order to fine-tune orphan drug legislation to maximise efficiency. The US and the EU enjoy a streamlined procedure for obtaining orphan drug designation that serves to simplify sponsor application in both territories and encourage orphan product development even further. Although in existence for a shorter period of time, the EMEA can inform the US of ways to accelerate productivity, while continuing to learn from the original orphan drug act pioneers, who initially found the way to bring relief for rare disease patients and continue to offer hope to many more.

National & International Policy Developments
New US clinical research programme to tackle undiagnosed rare disorders
Perhaps the most difficult of rare disease cases are those that have no diagnosis. Professionals, in addition to patients and their families, are baffled by the constellation of symptoms presented and unsure how to proceed with treatment and care. Now, the National Institutes of Health (NIH) in the US has unveiled an initiative of its Intramural Program. The Undiagnosed Diseases Program is a clinical research undertaking specifically designed for medical cases that elude diagnosis. The programme will investigate cases referred to the NIH Clinical Center (the largest hospital in the world totally dedicated to clinical research) by physicians across the country. The programme is designed to capitalise on the expertise of different NIH agencies, including the National Human Genome Research Institute (NHGRI), the NIH Office of Rare Diseases (ORD) and the NIH Clinical Center. Many medical specialties will contribute expertise to the programme, including expert physicians from the fields of rheumatology, immunology, oncology, mental health, nephrology, haematology, ophthalmology, laboratory medicine, neurology, pain and palliative care, bone disorders, endocrinology, dermatology, primary immunodeficiency, dentistry, genetics, pathology, pulmonology, cardiology, internal medicine, paediatrics, and hepatology. In a press release, NIH Director Elias A. Zerhouni stated that "the goal of NIH's Undiagnosed Diseases Program is two-pronged: to improve disease management for individual patients and to advance medical knowledge in general."

The programme is expected to be ready to receive its first patient as soon as July. It is anticipated that up to 100 patients will be admitted to the programme each year. The programme has strict eligibility criteria, designed to filter through only patients whose condition truly escapes diagnosis, and in this element lays perhaps the most difficult challenge of the new programme: how to discern genuinely undiagnosed conditions from those for which a diagnosis exists that is beyond the scope of experience or expertise of the referring health professional? The programme will collaborate with patient organisations, which can be vital in providing information and helping to discern eligible patients. The Genetic and Rare Diseases Information Center states that some 6% of inquiries received over the past three years were related to an undiagnosed condition. An earlier study reported that only 50% of rare disease patients received a diagnosis within a year. Some 15% of patients in this study waited over five years for a diagnosis.

Dr. William Gahl, NHGRI clinical director and an expert on rare genetic diseases, will serve as director of the Undiagnosed Diseases Program, working in conjunction with Dr. Stephen Groft, Director of the Office of Rare Diseases, and NIH Clinical Center director Dr. John Gallin. The NIH Clinical Center currently has more than 80,000 patients in nearly 1500 research studies. Approximately half of the patients has a rare disease. The added-value of the Undiagnosed Diseases Program lies in the fact that incoming patients will be assessed by a broad spectrum of medical experts rather than being triaged directly into one of the existing 1500 protocols. The new program will include patients who do not clearly fit into any protocol; in fact, it is likely that new protocols will ultimately be created. The Undiagnosed Diseases Program is intended primarily for US citizens and residents, but is open to overseas patients with compelling circumstances. Consult the FAQ sheet for the Undiagnosed Diseases Program


Ethical, Legal & Social Issues
Patient Rights in the EU – Spain and Portugal
The Centre for Biomedical Ethics and Law of the Catholic University of Leuven in Belgium, in collaboration with the European Commission and EuroGentest, has added two more ethical-legal documents on patient rights in the EU to its collection. Seeking to encourage transparency and facilitate the exchange of information between researchers both within Europe and further afield, these booklets provide an outline of the legislative frameworks and key patient rights in each country. Similar studies have already been produced for Bulgaria, Cyprus, Czech Republic, Denmark, Estonia, Greece, Hungary, Lithuania, Slovakia and Slovenia. Now Portugal and Spain join the collection – each of which has its own particular strengths, as well as areas for improvement. The booklets address a variety of issues, including personal data protection, genetic testing, discrimination, and informed consent – matters all relevant to rare disease patients, their families and their caregivers. The booklets are freely available online.
A new US law prohibits discrimination based on genetic information
New knowledge about the genetic basis of illness can allow for the earlier detection of illnesses, often before symptoms have begun. New knowledge about genetics can also allow for the development of better therapies that are more effective against disease or have fewer side effects than current treatments. However, advances in genetic testing have also given rise to the potential misuse of genetic information to discriminate in employment or health insurance. To combat this, US president George W. Bush has signed into law legislation that bans discrimination based on an individual’s genetic profile. Under the Genetic Information Nondiscrimination Act (GINA), health insurers are prohibited from requiring consumers to take a genetic test that might reveal a predisposition to a certain disease – including rare diseases, which often come with expensive medicinal treatments. The law also prevents health insurers from cancelling, denying, refusing to renew, or changing the terms or premiums of coverage based solely on a genetic predisposition toward a specific disease. Employers are also affected by the law and thus can no longer use genetic information in professional decision making such as hiring, promoting, or terminating employment. The legislation, which passed unanimously in the Senate, and by an overwhelming majority in the House of Representatives (414 to 1), is expected to reduce patient reluctance toward genetic testing.

Orphanet News
New Texts
New Orphanet Journal of Rare Diseases publications
LEOPARD syndrome

Deletion 22q13.3 syndrome


New Syndromes
3q29 interstitial microduplication: a new syndrome with mental retardation and microcephaly
Microdeletion and microduplication genetic syndromes are known to be a significant cause of developmental delay and dysmorphology. The authors identified a novel genomic syndrome comprising of an interstitial duplication of approximately 1.61 Mb at the distal end of chromosome 3 band q29. The imbalance was present in five individuals in a three generation family with clinical features including mild to moderate mental retardation and microcephaly.
Read the PubMed abstract

Am J Med Genet A ; 601-609 ; March 2008
Autosomal-recessive mental retardation with retinitis pigmentosa in a consanguineous family
Autosomal-recessive inheritance is believed to be relatively common in mental retardation, although only four genes for nonsyndromic autosomal-recessive mental retardation (ARMR) have been reported. In this study, the authors ascertained a consanguineous Pakistani family with ARMR in four living individuals from three branches of the family, plus an additional affected individual later identified as a phenocopy. Retinitis pigmentosa was present in affected individuals. A homozygous mutation was found in gene CC2D2A, thought to have a possible role in Ca(2+)-dependent signal transduction.
Read the PubMed abstract

Am J Hum Gen ; 1011-1018 ; April 2008
Autosomal-recessive microtia, hearing impairment, and partial cleft palate: A mutation in HOXA2 is responsible
Microtia, a congenital deformity manifesting as an abnormally shaped or absent external ear, occurs in one out of 8,000-10,000 births. The authors ascertained a consanguineous Iranian family segregating with autosomal-recessive bilateral microtia, mixed symmetrical severe to profound hearing impairment, and partial cleft palate. They found a punctual mutation in gene HOXA2, whose role in auditory-system development has already been demonstrated in mouse models.
Read the PubMed abstract

Am J Hum Gen ; 982-991 ; April 2008
Nagashima-type keratosis as a novel entity in the palmoplantar keratoderma category
Nagashima-type keratosis is characterised by transgressive and nonprogressive palmoplantar keratoderma (PPK) with an autosomal recessive trait. Because its clinical manifestations are similar to but milder than those of mal de Meleda, it was originally described as a mild form of Meleda-type PPK. Since then, about 20 cases have been reported in the Japanese-language literature. The authors report a 17-year-old boy presenting with transgressive, hyperhidrotic, erythematous, and hyperkeratotic lesions on his palms and soles that had developed when he was an infant. The symptoms and clinical course were typical for Nagashima-type PPK. A genetic study was performed to search for a mutation in the SLURP1 gene, which is responsible for mal de Meleda, but no mutations were detected in the exon or intron sites of SLURP1, suggesting that Nagashima-type keratosis is a novel entity of PPK and is distinct from mal de Meleda.
Read the PubMed abstract

Arch Dermatol ; 375-379 ; March 2008

New Genes
Two forms of X-linked mental retardation linked to SLC9A6 mutations
Linkage analysis and DNA sequencing in a family exhibiting an X-linked mental retardation (XLMR) syndrome, characterised by microcephaly, epilepsy, ataxia, and absent speech and resembling Angelman syndrome, identified a deletion in the SLC9A6 gene encoding the Na(+)/H(+) exchanger NHE6. Subsequently, other mutations were found in a male with mental retardation who had been investigated for Angelman syndrome and in two XLMR families with epilepsy and ataxia, including a family designated as having Christianson syndrome.
Read the PubMed abstract

Am J Hum Gen ; 1003-1010 ; April 2008
Familial Parkinson disease: Mutations in the GIGYF2 gene at the PARK11 locus identified
The molecular basis for association of the PARK11 region of chromosome 2 with familial Parkinson disease (PD) is unknown. This study examined the GIGYF2 gene, which contains the PARK11 microsatellite marker displaying the highest linkage score. The 27 coding exons of the GIGYF2 gene were sequenced in 123 Italian and 126 French patients with familial PD. A total of seven different missense mutations resulting in single amino acid substitutions were present in 12 patients. These data strongly support GIGYF2 as a PARK11 gene with a causal role in familial PD.
Read the PubMed abstract

Am J Hum Gen ; 822-833 ; April 2008
Arrhythmogenic right ventricular cardiomyopathy type 5: a mutation in the TMEM43 gene at locus ARVD5 is at cause
Autosomal-dominant arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) causes sudden cardiac death and is characterised by clinical and genetic heterogeneity. The authors have identified a mutation in gene TMEM43 at locus ARVD5. They conclude that ARVC at locus ARVD5 is a lethal, fully penetrant, sex-influenced morbid disorder. Although little is known about the function of the TMEM43 gene, it contains a response element for PPAR gamma (an adipogenic transcription factor), which may explain the fibrofatty replacement of the myocardium, a characteristic pathological finding in ARVC.
Read the PubMed abstract

Am J Hum Gen ; 809-821 ; April 2008

Research in Action
Fundamental Research
Spinocerebellar ataxia type 1: opposing effects of polyglutamine expansion on native protein complexes contribute to the diseas
Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative disease caused by expansion of a glutamine repeat in ATXN1. The mechanism by which this occurs remains enigmatic, as the mutant protein apparently maintains interactions with its usual partners. Here the authors show that the expanded polyglutamine tract differentially affects the function of the host protein in the context of different endogenous protein complexes. Polyglutamine expansion in ATXN1 favours the formation of a particular protein complex containing RBM17, contributing to SCA1 neuropathology by means of a gain-of-function mechanism. Concomitantly, polyglutamine expansion attenuates the formation and function of another protein complex containing ATXN1 and capicua, contributing to SCA1 through a partial loss-of-function mechanism.
Read the PubMed abstract

Nature ; 713-718 ; April 2008
Clinical Research
A variety of phenotypes are associated with loss of nephrocystin-3 function
The authors use a combinatorial approach in mice and humans to define the phenotypic spectrum of NPHP3/Nphp3 mutations and the role of the nephrocystin-3 protein. They show that mutations in the gene encoding nephrocystin-3 protein can cause a broad clinical spectrum of early embryonic patterning defects comprising situs inversus, polydactyly, central nervous system malformations, structural heart defects, preauricular fistulas, and a wide range of congenital anomalies of the kidney and urinary tract.
Read the PubMed abstract

Am J Hum Gen ; 959-970 ; April 2008
Muir-Torre syndrome frequently associated with Lynch syndrome
Lynch syndrome is characterised by a predisposition to visceral malignancies associated with deleterious germline mutations in DNA mismatch repair genes. Muir-Torre syndrome has a predisposition to certain skin tumours. The authors determined the frequency of Muir-Torre syndrome among 50 Lynch syndrome families: Muir-Torre syndrome was observed in 28% of families and in 9.2% of individuals with Lynch syndrome. Four of nine families with MLH1 mutations had a member with Muir-Torre syndrome compared with 10 of 24 families with MSH2 mutations. Families who carried the c.942+3A>T MSH2 gene mutation had a higher frequency of Muir-Torre syndrome than families who carried other mutations in the MSH2 gene (75% vs 25%). Muir-Torre syndrome was not found in families with mutations in the MSH6 or PMS2 genes. These results suggest that Muir-Torre syndrome is a variant of Lynch syndrome. Screening for Muir-Torre syndrome-associated skin lesions among patients with Lynch syndrome is recommended.
Read the PubMed abstract

J Natl Cancer Inst ; 277-281 ; February 2008
Steinert disease: larger expansions correlate to more severe cognitive deficit
Steinert disease, also known as myotonic dystrophy type 1, is a muscle disease characterised by myotonia and by multiorgan damage that combines various degrees of muscle weakness, arrhythmia and/or cardiac conduction disorders, cataract, endocrine damage, sleep disorders and baldness. The disease is associated with abnormalities at the 19q13-2 locus (abnormally high CTG triplet repetition).The authors assessed the cognitive profile in the childhood-onset form of myotonic dystrophy. The results highlighted a negative correlation between the CTG repeat size and cognitive function: 55% of the subjects studied presented large CTG expansion correlated with significant extensive cognitive deficits.
Read the PubMed abstract

Neuromuscul Disord ; 451-458 ; June 2007
Acute lymphoblastic leukaemia and acute myeloid leukaemia: NF1 inactivation is frequent
Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder caused by mutations in the NF1 gene. Patients have a higher risk of developing juvenile myelomonocytic leukaemia with a possible progression toward acute myeloid leukaemia. In an oligo array comparative genomic hybridization-based screening of 103 patients with paediatric T-cell acute lymphoblastic leukemia (T-ALL) and 71 patients with MLL-rearranged acute myeloid leukaemia, a recurrent cryptic deletion, del(17)(q11.2), was identified in 3 patients with T-ALL and 2 patients with MLL-rearranged AML. This deletion has previously been described as a microdeletion of the NF1 region in patients with NF1. However, the patients in this study lacked clinical NF1 symptoms. Mutation analysis in 4 of these del(17)(q11.2)-positive patients revealed that mutations in the remaining NF1 allele were present in 3 patients, confirming its role as a tumour-suppressor gene in cancer.
Read the PubMed abstract

Blood ; 4322-4328 ; April 2008
Factor XI deficiency: reduced incidence of ischemic stroke
The authors investigated the incidence of ischemic stroke in patients with severe inherited factor XI deficiency. They found that severe factor XI deficiency probably is protective against ischemic stroke but not against acute myocardial infarction.
Read the PubMed abstract

Blood ; 4113-4117 ; April 2008
Therapeutic Approaches
Cystic fibrosis: PTC124 promotes suppression of the human CFTR-G542X nonsense allele in mouse models
Nonsense mutations inactivate gene function and are the underlying cause of a large percentage of the individual cases of many genetic disorders. PTC124 is an orally bioavailable compound that promotes readthrough of premature translation termination codons, suggesting that it may have the potential to treat genetic diseases caused by nonsense mutations. Using a mouse model for cystic fibrosis, the authors show that injection or oral administration of PTC124 to Cftr-/- mice expressing a human CFTR-G542X transgene suppressed the G542X nonsense mutation and restored a significant amount of human (h)CFTR protein and function. In light of its oral bioavailability, safety toxicology profile in animal studies, and efficacy with other nonsense alleles, PTC124 has the potential to be an important therapeutic agent for the treatment of inherited diseases caused by nonsense mutations.
Read the PubMed abstract

Proc Natl Acad Sci U S A ; 2064-2069 ; February 2008
Diagnostic Approaches
Juvenile polyposis syndrome: genomic deletions explain 15% of cases
Juvenile polyposis syndrome (JPS) is a rare autosomal dominant disorder characterised by multiple gastrointestinal juvenile polyps and an increased risk of colorectal cancer. This syndrome is caused by germline mutation of either SMAD4 or BMPR1A, and possibly ENG. PTEN, originally linked to Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome, has also been associated with JPS. In this study, a comprehensive genetic analysis of SMAD4, BMPR1A, PTEN and ENG was performed through direct sequencing and multiplex ligation-dependent probe amplification (MLPA) in JPS patients. Large genomic deletions of SMAD4, BMPR1A and PTEN are a common cause of JPS. Using direct sequencing and MLPA, a germline defect was detected in 48.1% of JPS patients. MLPA identified 14.8% of these mutations. Since a substantial percentage of JPS patients carry a germline deletion and MLPA is a reliable and user-friendly technique, it is concluded that MLPA is a valuable adjunct in JPS diagnosis.
Read the PubMed abstract

Gut ; 623-627 ; May 2008

Patient Management and Therapy
Fabry disease: fabrazyme is safe and effective in children
Fabry disease is a genetic disorder in which deficient endogenous enzyme causes pathogenic tissue accumulation of globotriaosylceramide. Fabrazyme (agalsidase beta) is an orphan medicinal product authorised in Europe since 2001. The authors report an open-label study involving 16 patients aged eight through 16 years. Agalsidase beta safely and effectively reduced the GL-3 accumulation in dermal endothelium already evident in children with Fabry disease. Early intervention may prevent irreversible end-organ damage from chronic GL-3 deposition.
Read the PubMed abstract

J Pediatr ; 563-570 ; April 2008
Ullrich congenital muscular dystrophy and Bethlem myopathy: cyclosporin A corrects mitochondrial dysfunction and muscle apoptos
Ullrich congenital muscular dystrophy and Bethlem myopathy are skeletal muscle diseases caused by mutations in the genes encoding collagen VI. Myoblasts from patients affected by Ullrich congenital muscular dystrophy display functional and ultrastructural mitochondrial alterations and increased apoptosis due to inappropriate opening of the permeability transition pore, a mitochondrial inner membrane channel. These alterations could be normalised by treatment with cyclosporin A, a widely used immunosuppressant that desensitizes the permeability transition pore independently of calcineurin inhibition. Here, the authors report the results of an open pilot trial with cyclosporin A in five patients with collagen VI myopathies. Before treatment, all patients displayed mitochondrial dysfunction and increased frequency of apoptosis, as determined in muscle biopsies. Both of these pathologic signs were largely normalised after 1 month of oral cyclosporin A administration, which also increased muscle regeneration.
Read the PubMed abstract

Proc Natl Acad Sci USA ; 5225-5229 ; April 2008
Sickle cell anaemia: senicapoc increases haemoglobin concentration
In a 12-week, multicenter, phase 2, randomized, double-blind, dose-finding study, the authors evaluated senicapoc's safety and its effect on hemoglobin level and markers of red blood cell hemolysis in sickle cell anaemia patients. Senicapoc was safe and well tolerated. The increased hemoglobin concentration and concomitant decrease in the total number of reticulocytes and various markers of red blood cell destruction following senicapoc administration suggests a possible increase in the survival of sickle red blood cells. Senicapoc received an orphan designation in the USA in March 2000.
Read the PubMed abstract

Blood ; 3991-3997 ; April 2008
Familial adenomatous polyposis: clinical management guidelines
Familial adenomatous polyposis (FAP) is an inherited syndrome responsible for <1% of all colorectal cancer (CRC) cases. The syndrome is characterised by the development of hundreds to thousands of adenomas in the colorectum. Almost all patients will develop CRC if they are not identified and treated at an early stage. The syndrome is inherited as an autosomal dominant trait and caused by mutations in the APC gene. Recently, a second gene has been identified that also gives rise to colonic adenomatous polyposis, although the phenotype is less severe than typical FAP. The gene is the MUTYH gene and the inheritance is autosomal recessive. In April 2006 and February 2007, a workshop was organised in Mallorca by European experts on hereditary gastrointestinal cancer aiming to establish guidelines for the clinical management of FAP and to initiate collaborative studies. Thirty-one experts from nine European countries participated in these workshops. Prior to the meeting, various participants examined the most important management issues according to the latest publications. During the workshop, all recommendations were discussed in detail. Because most of the studies that form the basis for the recommendations were descriptive and/or retrospective in nature, many of them were based on expert opinion. The guidelines described herein may be helpful in the appropriate management of FAP families. In order to further improve the care of these families, prospective controlled studies should be undertaken.
Read the PubMed abstract

Gut ; 704-713 ; May 2008

Orphan Drugs
Five EMEA orphan drug designations for May

The COMP (Committee for Orphan Medicinal Products) adopted the following five positive opinions on orphan medicinal product designation at its May meeting for the treatment of:

- acute lymphoblastic leukaemia
- pulmonary arterial hypertension
- cystic fibrosis
- myelodysplastic syndrome
- acute myeloid leukaemia
Consult the European Registry for Orphan designations
Consult the Orphanet list of orphan drugs authorised for marketing in Europe


News from the Patients' Associations
Eurordis appraises the efforts of its volunteers: priceless!

At the recent annual Membership Meeting of the European Organisation for Rare Diseases (Eurordis) that took place 16-17 May in Copenhagen, the contribution of volunteers who donate their time and particular talents was assessed and appraised. Eurordis, a patient-driven alliance of patient organisations and individuals active in the field of rare diseases, calculated that its 180 volunteers contributed 916 days valued at 377,000 euros to Eurordis activities in 2007. This was audited and certified by Deloitte, an international tax, audit and financial consulting firm. In particular, 15 volunteers specifically dedicated to advocacy action at the European level contributed 397 days. Other volunteers were either translators or involved in European projects. Eurordis, a not-for-profit organisation with a stringent financial transparency policy, defines its overall mission as building a pan-European community of patient organisations and individuals with rare diseases in order to work together to improve the quality of life for patients and their families. The organisation has several ongoing projects geared toward building patient solidarity and improving access to medicinal products and care. The Eurordis volunteer assessment acknowledged gratefully that the generosity and talents of its volunteers are essential to the ongoing success of the organisation’s projects and activities. Current volunteer opportunities with Eurordis


Courses & Educational Initiatives
Advanced Course on Epidemiological, Clinical and Genomic Databases
This workshop, held from 7-12 July, 2008 in Milan, Italy addresses topics including medical records; clinical databases; genomic databanks; epidemiological archives and registers; medical data integration; hospital and health information systems; telecommunication and networking infrastructures; internet in biomedicine; methods of data analysis (classification, clustering, discriminant, regression); and more. For further information
Practical Biobanking Course
Nowgen, A Centre for Genetics in Healthcare, is hosting a 2nd Practical Biobanking Course in partnership with the Centre for Integrated Genomic Medical Research (CIGMR) at The University of Manchester and the UK DNA Banking Network. The first workshop, held at the Nowgen Centre in November 2007, was a great success, attracting 45 delegates from 14 different countries.

This second two day intensive course, taking place 30 June-1 July, is designed for both biobank sponsors and researchers looking to establish and maintain a biological sample resource. The emphasis of the course will be on the practical aspects of establishing and running a successful biobank. For further information

European Advanced Postgraduate Course in Classical and Molecular Cytogenetics - 2009
The course is designed to provide medical graduates, pharmacists, researchers, graduate students and health professionals with advanced training in constitutional, haematological, and oncological cytogenetics. The students will be trained to identify genetic abnormalities using both classical and molecular cytogenetic techniques for diagnosis, prognosis, and fundamental and applied research. The course is co-organised by the European Cytogenetists Association and two French Universities, either as a stand-alone course with only the theoretical part or as a University Diploma including both theoretical and practical training. For further information
A unique online MSc course in haemoglobinopathies
Thalassaemia International Federation (TIF) in collaboration with University College London (UCL) is offering a unique online MSc course in Haemoglobinopathies. The first e-learning course in this field, the course offers health professionals the opportunity to pursue an advanced degree from anywhere in the world. For further information

What's on Where?
5th International Conference on Alpha1-antitrypsin Deficiency
Date: 10 June 2008
Venue: Birmingham, UK

Conference sessions will include genetic and environmental factors, screening, and treatment approaches.
For further details

Geneskin: Towards a Better Understanding and Care of Genetic Skin Diseases
Date: 20 June 2008
Venue: Rome, Italy

The final meeting of the EU funded Coordination Action project “Rare genetic skin diseases: advancing diagnosis, management and awareness through a European network” includes talks by both members of the GENESKIN consortium and invited speakers on the most recent advances in research, diagnosis, therapy and management of inherited skin diseases. Registration is free.
For further details

5th International Cystinosis Conference
Date: 27-28 June 2008
Venue: Dublin, Ireland

World experts in the field of Cystinosis will attend and the latest research in this very rare disease will be presented. The event is unique as it combines a high-level scientific and medical conference as well as being a family and patient friendly conference.
For further details

15th International Paediatric Colorectal Club Meeting
Date: 29 June- 1 July 2008
Venue: Salamanca, Spain

For further details

Fourth International Neuroacanthocytosis Symposium: Bridging Clinical and Basic Aspects
Date: 1-2 July 2008
Venue: Oxford and London, England

Including clinical aspects of chorea acanthocytosis and McLeod syndrome, muscle and nerve neuropathology and syndromes related to NA. View the programme.
For further details

15th Retina International World Congress
Date: 4-5 July 2008
Venue: Helsinki, Finland

Clinical diagnostics of retinal dystrophies, genetic diagnostics and research, Usher syndrome, ongoing clinical trials.
For further details

Supporting Policy Development in Genomics Symposium
Date: 6 July 2008
Venue: Montreal, Canada

Policy-makers and researchers from a variety of fields are convened to this international symposium in view of outlining a roadmap towards a more concerted research approach to inform policy.
For further details

New and Developing Technologies for Genetics Diagnostics
Date: 7-8 July 2008
Venue: Salisbury, UK

This meeting will cover a wide range of techniques and issues relevant to genetic diagnostics in the 21st century. The meeting will focus on new sequencing technologies, non-invasive prenatal diagnosis, molecular cytogenetics copy number determination.
For further details

Fourth International Conference on Metals and Genetics
Date: 21-24 July 2008
Venue: Paris, France

The main topics will include metal-associated diseases: molecular and systemic biology approaches; characterisation and speciation of metal in proteins and biological tissues; and metals and environmental health implications.
For further details

Barth Syndrome: On Track Toward a Cure - 4th International Conference
Date: 21-26 July 2008
Venue: Florida, USA

This conference will be dedicated to increasing knowledge and accelerating advances in research for this rare metabolic genetic disorder. It will bring together basic scientists, clinical researchers, treating physicians, other professionals, and affected individuals and families to focus on the syndrome through a series of carefully organised sessions.
For further details

Inaugural Birt Hogg Dube Syndrome Symposium
Date: 3 September 2008
Venue: Roskilde, Denmark

Laboratory research session in the morning and a clinical session in the afternoon. Keynote presentation and opportunity for a number of short talks in each session. There will be poster presentations. This is an opportunity for researchers and clinicians to present their work, share ideas and set up collaborations to promote BHD research and to establish screening guidelines for BHD patients. Deadline for abstract submission is 15 June, 2008.
For further details

6th International Conference on Frontotemporal Dementia
Date: 3-5 September 2008
Venue: Rotterdam, The Netherlands

Symposium highlights include: Caregivers burden; Early onset dementia AD; Genetic Counseling; Aphasic syndromes; Tau; Progranulin; TDP-43 protein; Genetics of the FTD; ALS spectrum; Animal and Cell Models; Neuropathology and biochemistry of FTD; Clinical spectrum FTD; Pharmacological treatments; and more.
For further details

15th Paediatric Rheumatology European Society Congress
Date: 14-17 September 2008
Venue: University College London, UK

The programme will cover four main topics through keynote lectures, abstract presentations and educational workshops: juvenile arthritis, juvenile dermatomyositis, vasculitis and pain. There will be novel symposia such as sport and exercise in young people.
For further details

2nd Congress of Ring14 International Association for Rare Neurogenetic Diseases Research
Date: 25-27 September 2008
Venue: Reggio Emilia, Italy

An interesting and varied programme for professionals, patients and their families.
For further details

13th International Meeting of the World Muscle Society
Date: 29 September-2 October 2008
Venue: Newcastle upon Tyne, UK

New Insights into the pathogenesis of facioscapulohumeral muscular dystrophy, myotonic dystrophy and other dominant muscular dystrophies, Advances in the understanding and treatment of myasthenic disorders, Therapeutic advances in neuromuscular disorders, Advances across the neuromuscular field, including treatment and management.
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International Conference on Thalassaemia and Haemoglobinopathies
Date: 8-11 October 2008
Venue: Singapore

The 11th International Conference on Thalassaemia and Haemoglobinopathies and the 13th International Thalassaemia TIF Conference for Thalassaemia Patients and Parents. "Equal Access to Quality Medical Care for Every Patient with Thalassaemia" is the theme of this year's conferences.
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6th World Rett Syndrome Congress
Date: 10-13 October 2008
Venue: Paris, France

Various aspects of Rett syndrome and MECP2 functioning, including fundamental, clinical and management topics.
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Tenth International Meeting on Osteogenesis Imperfecta
Date: 15-18 October 2008
Venue: Ghent, Belgium

Topics include: Bone homeostasis, murine models/collagen biology/biophysics, classification, genetics: genotype-phenotype, prenatal diagnosis/preimplantation diagnosis, biphosphonates, orthopedic management, hearing loss: physiopathology, surgery and imaging, other medical management issues, stomatology/dentistry, psychosocial aspects, new (therapeutic) perspectives.
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EPPOSI 9th Workshop on Partnering for Rare Diseases Therapy Development
Date: 16-17 October 2008
Venue: Paris, France

Mark your calendars for the 2008 EPPOSI workshop, taking place at the National Assembly in Paris. The theme of the workshop is Orphan drugs: partnering along the chain and across the borders - Sharing strategies and tools for access to diagnosis and treatment.
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Rare Tumors in Europe: Challenges and Solutions
Date: 6 November 2008
Venue: Brussels, Belgium

Details to follow shortly.
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Press & Publications
Genetics in Medicine journal publishes several articles on rare disease testing
Genetics in Medicine, the journal of the American College of Medical Genetics, has included in its May issue a series of articles dedicated to genetic testing concerns in relation to rare diseases. Included in the issue are the articles Issues in genetic testing for ultra-rare diseases: background and introduction; Gene patenting and licensing: the role of academic researchers and advocacy groups; New quality assurance standards for rare disease testing; Developing a national collaborative study system for rare genetic diseases; Molecular genetic testing for ultra rare diseases: models for translation from the research laboratory to the CLIA-certified diagnostic laboratory; Molecular testing: improving patient care through partnering with laboratory genetic counsellors; and A model program to increase translation of rare disease genetic tests: collaboration, education, and test translation program. These articles address several hot topics that are currently being explored and debated on both sides of the Atlantic.
Consult the table of contents of Genetics in Medicine

European rare disease conference report released
The conference report from the Fourth European Conference on Rare Diseases held last November in Lisbon has been released and is freely available online or in a book format that can be ordered. The conference gathered over 400 participants from some 35 countries, working together to coordinate and harmonise efforts to address the needs of rare disease patients and their families. The programme featured presentations, debates, poster sessions, and a pre-conference workshop. The conference, organised by the European Organisation for Rare Diseases, allowed for an exchange between patients, healthcare professionals, industry representatives, and policy makers from individual Member States and at the European level. The report is organised into a series of chapters that address European policy, research and networks, new treatments and orphan drug development, information services, patient-driven projects, patient needs beyond medical care, and recent advancements. The report also includes a rich array of abstracts and recent statistics, and is presented in an attractive illustrated format.
View the conference report online
Order a copy of the conference report


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: Ségolène Aymé
Editor: Louise Taylor
Contact Us
Editorial Board: Ségolène Aymé, Catherine Berens, Helen Dolk, Anders Fasth, Laura Fregonese, Edmund Jessop, Matthieu Levi-Strauss, Jordi Llinares-Garcia, Antoni Montserrat, Annie Olry, Manuel Posada de la Paz, Ewa Pronicka, Claire Scharf-Kroener, Janos Sandor, Domenica Taruscio, Paloma Tejada, T.O.F. Wagner
For more information on the Rare Diseases Task Force
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