31 March 2015 print
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Austria adopts its National Action Plan for Rare Diseases

Austria has recently adopted its National Action Plan for Rare Diseases which is called NAP.se. The NAP.se was commissioned by the Federal Ministry of Health of Austria (BMG) in collaboration with two advisory bodies - Group of Experts on Rare Diseases (since 2014 Advisory Board for rare diseases) and Strategic Platform for Rare Diseases.

The NAP.se contains nine key topics that take into account both the European recommendations and national needs. These are the following:
- Documentation of rare diseases in the health and social system
- Improvement of medical-clinical care of rare disease sufferers
- Improving the diagnosis of rare diseases
- Improving the treatment of and access to treatments for rare diseases
- Research in the field of rare diseases
- Improving knowledge and awareness of rare diseases
- Improving epidemiological knowledge in the context of rare diseases
- Establishment of permanent consultative bodies for rare diseases in BMG
- Recognition of the benefits of self-help

With regard to caring for rare disease patients, the focus of NAP.se is on the better coordination of clinical care by designating centres of expertise and their subsequent crosslinking within Austria as well as their integration into European Reference Networks. The aim of the NAP.se is not to create new structures, but join in on regional centres of expertise that meet certain quality and performance criteria. In order to provide patients with a speedy confirmed diagnosis, the NAP.se calls for the introduction of uniform standards in Austria as well as pooling of expertise from other regions.

The implementation process of NAP.se and its success will be verified by appropriate monitoring. Diversity and complexity of the measures require that the definition of indicators is an active process for the implementation of each operation. This ensures that current developments and adaptations are met as required.
Read the Austrian National Action Plan for Rare Disease (NAP.se) in German

EC Expert Group
Commission Expert Group on Rare Diseases meeting: flash report available
The European Commission Expert Group on rare diseases met for the 4th time on 12-13 March, 2015. The main topics of discussion included:
- implementation of the European Reference Networks (ERNs)
- update on the development of pharmaceutical legislation and paediatric clinical trials
- rare disease registries
- genetic testing
Draft recommendations for cross-border genetic testing and an addendum to the 2013 EUCERD recommendations on ERN's for rare diseases were discussed and will be further revised prior to adoption at the next expert group meeting which will be held on 10-11 June 2015.
The Flash report is now available on the European Commission website


National & International Policy Developments
Other European news
Update on EUCERD Joint Action activities

EUROPLAN National Conferences: majority of conference reports available online
The EUROPLAN work package in the context of the EUCERD Joint Action, has provided support to the development and implementation of national rare disease plans, notably through the organisation of national conferences in the majority of Member States.

The conferences, organised by National Alliances of rare disease patient organisations under the supervision of EURORDIS and Istituto Superiore di Sanita, focus on challenges experienced during the adoption and implementation of national plans and on how to turn national plan provisions into a reality that positively impacts the everyday life of people living with a rare disease. Reports from 20 out of 24 EUROPLAN National Conferences are now available on the EURORDIS website which address the challenges mentioned above in the respective member states in areas that are delineated by the work package.
Read the EUROPLAN conference reports

Report: EUCERD joint action workshop on the guiding principles for social care in rare diseases
Building supportive social care structures for the holistic care of rare disease patients and their families is essential to their empowerment. Providing holistic care for rare disease patients is not without challenges in Europe, as care pathways remain very complex with an urgent need to compile guiding principles for social care. To address these issues, the EUCERD Joint Action workshop on the guiding principles for social care in rare diseases was held recently.

The main objective of the workshop was to build consensus on a list of priority issues to be included in the draft Recommendations of the Commission Expert Group of Rare Diseases (CEGRD) on Social Care for Rare Diseases. The workshop participants highlighted the importance of providing coordination and networks of care providers, of establishing case manager services, of putting into place training schemes for social services providers and patients, delivering better assessment of disability/ability, and disseminating information on good practices. These propositions will be the basis of a proposal for a CEGRD draft Recommendations on Social Care for Rare Diseases which will be discussed by the CEGRD later in the year.

The workshop report and all the presentations are now available online, while the draft recommendations will be made available before the end of August 2015.
Read the workshop report

Access to orphan drugs and budget impact in Bulgaria
A recent document published an annual “analysis of access to orphan drugs in Bulgaria, budget impact of medicinal therapies for rare diseases and good practices for rare disease patient access to orphan drugs in the EU has been published”. The document emphasised that there is an impetus to improve access to rare disease therapies in Bulgaria, even though it is currently limited compared to other EU member states. The analysis demonstrates that while the inclusion of mandatory health insurance coverage for rare disease patients has proved to be useful, there has not been an adverse budget impact on the health insurance model in Bulgaria. The document highlights the importance of collecting national epidemiological, clinical and economic data in rare disease registers. The analysis concluded that the implementation of risk-sharing agreements will optimise planning and management of public expenditure for rare disease therapies in Bulgaria.
Read the report

Ireland’s first National Rare Disease Office (NRDO) is expected to open officially in a number of months
Ireland’s first National Rare Disease Office (NRDO) is expected to open officially in a number of months, the HSE has stated. The establishment of a NDRO was one of the key recommendations of the Department of Health’s first national rare disease plan, ‘A Rare Disease Plan for Ireland 2014-2018’, which was published last July. The new office will be responsible for building information on the availability of expertise in Ireland for rare diseases and making this available to patients and doctors. It will also establish a helpline for patients with access to a genetic counsellor and support the HSE in the mapping and validation of centres of expertise in rare diseases in Ireland, as well as having a long term role in rare diseases surveillance. HSE is currently designating existing centres of expertise for the diagnosis, care, clinical research and training in rare diseases according to accepted European criteria.

Other International News
Estimation of prevalence of rare diseases in China from the perspective of return on investment
The authors of an article published in the Orphanet Journal of Rare diseases address the issue of deciding on a threshold to define diseases as rare. The authors believe that this is especially important to create legislation needed for orphan drug designation in China. According to the authors, “without incentives, it is unlikely that domestic Chinese pharmaceutical companies will cover the costs of bringing an orphan drug to market”.

They suggest an approach to define rare diseases for China based on the return on investment of innovative (orphan) drugs. The authors estimated the research and development costs per innovative drug to be $1.2 billion, where sales per new drug should reach about $15–24 billion to recuperate its research and development costs and generate profit. Finally, the authors took into account the reimbursement ceiling in China, which is $50,000 annually per person. From these extrapolations, the authors estimated that at least 300,000–500,000 (about 2–4 out of 10,000, based on the Chinese population of 1.35 billion) rare disease patients, a number higher than US and EU, are needed per drug to guarantee the return on investment and ensure profit incentives for further research and investor support.
Read the open access article

IRDiRC recommended: an indication of quality in rare diseases research
The International Rare Diseases Research Consortium (IRDiRC) was set up to accelerate R&D in the field of rare diseases diagnostics and therapies so as to ensure that most rare diseases will have a diagnostic test by 2020 and that at least 200 new therapies for these diseases will reach the market by that date.

Among the many initiatives which were identified as key to contributing to such goals is the creation of a label to highlight key resources which, if used more broadly, would accelerate the pace of discoveries and translation into clinical services. Selected platforms/tools/standards/guidelines must be of fundamental importance to the rare diseases research and development community.

“IRDiRC Recommended” is a quality indicator, based on a specific set of criteria. Any platform/tool/ standard/guideline compliant with the criteria set forth is entitled to the label.

“IRDiRC Recommended” is a public label which could, and should, be made visible on and by the resource, giving the users a certain guarantee of its quality/appropriateness. IRDiRC encourages the long-term sustainability of the tools/standards/guidelines and their societal value. The application for “IRDiRC Recommended” is open to all project leaders wishing to obtain endorsement by IRDiRC of a platform/tool/standard/guideline that potentially contributes to the acceleration of R&D in the field of rare diseases. Commercial products are not eligible.
More information on the IRDiRC website

FDA formalises expedited review procedures for marketing applications with breakthrough therapy-designated drugs and biologics
Recently, the United States Food and Drug Administration (US FDA) confirmed that it has been informally instituting a policy to expedite the review of certain breakthrough therapy-designated applications for the past several months. FDA’s informal policy has now found its way into a Manual of Policies and Procedures (MAPP) entitled Under this pathway, FDA review teams are instructed to plan to act at least one month prior to the Prescription Drug User Fee Act (PDUFA) goal date. FDA’s MAPP describes the characteristics that breakthrough therapy-designated drugs eligible for “expedited review” should have. These include a demonstration of substantial improvement over existing therapies, designation for priority review, and a determination by the review team for a first cycle approval to be likely. Not all breakthrough therapy-designated drugs will receive expedited review as decisions will be made on a case-by-case basis. The MAPP also explains that the Center for Drug Evaluation and Research (CDER) review teams can determine that an expedited review is no longer appropriate and change the review to the default priority review timeline.
Read the Manual of Policies and Procedures

Use of Electronic Informed Consent in Clinical Investigations : guidance document by FDA Open for public consultation
New guidance issued by the United States Food and Drug Administration (FDA) could make it easier for companies to conduct clinical trials by explaining how federal regulators will permit companies to use electronic media like interactive websites to help facilitate the informed consent process. The guidance provides recommendations for clinical investigators, sponsors, and institutional review boards (IRBs) on the use of electronic media and processes to obtain informed consent for FDA-regulated clinical investigations of medical products, including human drug and biological products, medical devices, and combinations thereof. According to the FDA as long as the information provided is "adequate" and "understandable”, using a variety of methods to convey informed consent should be acceptable.
This guidance document is open for public consultation until 60 days after its publication on 3 March, 2015.
Read the draft document
Submit electronic comments to http://www.regulations.gov

Guidance Documents and Recommendations
Childhood cancer: recommendations for cardiomyopathy surveillance for survivors
Consult the Pubmed abstract
Lancet Oncol. ; 16(3):e123-e136 ; March 2015
Bioinformatics, Registries and Data Management
Challenges and bottlenecks for genomic data sharing
An article published in Applied & Translational Genomics, addressed the issues hindering efficient and ethical genomic data sharing in the human genomics research community. This investigation, conducted by the DNAdigest, included qualitative interviews followed by an online survey. The interviews identified four bottlenecks for data sharing which includes finding relevant and usable data (data discovery), getting authorisation to access data, formatting data as well as storing and moving data. Depending on the field, researchers cited either lack of time or potential loss of future publications as some of the reasons for not making more of their own data available to others even when they have the authority and consent to do so. A lack of sufficient resources to make their data available was also a oft expressed concern by these researchers.

The results of the online survey, containing questions that addressed the issues identified through the interviews, showed very good agreement with the findings described above. According to the authors, “it is important to continuously assess available solutions which facilitate data sharing/access and promote the mechanisms and practices that make the greatest impact”.
Read the open access article

CoBRA: guidelines to standardise the citation of bioresources in journal articles
One of the challenges involved in sharing bioresources (biological samples, data, and databases) is the lack of structural guidance to correctly recognise and trace their use especially in publications. An article published in BMC Medicine proposes, a guideline for reporting bioresource use in research articles, named CoBRA (Citation of BioResources in journal Articles). Developed by the members of the journal editors subgroup of the Bioresource Research Impact Factor (BRIF), CoBRA provides a citation system where “each individual bioresource that is used to perform a study and that is mentioned in the Methods section should be cited as an individual “reference [BIORESOURCE]” according to a delineated format”. Additionally, the European Association of Science Editors has adopted BRIF’s suggestion to incorporate statements on biobanks in the Methods section of their guidelines. According to the authors “ The endorsement and the adoption of the CoBRA guideline by authors, editors, researchers, and bioresource policy stakeholders is the first necessary step to achieve these goals and is essential to enhance transparency in health research”.
Read the open access article

Practical guidance on informed consent for paediatric participants in a biorepository
Mayo Clinic Proceedings has published a guidance document on obtaining informed consent from paediatric population to participate in a biorepository. Practices have become more complex, the task of developing appropriate informed consent practices has become more challenging. Written on behalf of the Consent, Education, Regulation, and Consultation Workgroup of the eMERGE Network, this document addresses the unique issues that arise for biorepositories that aim to collect samples from paediatric participants as a guidance for investigators and institutional review board (IRB) members in the United States regulatory context. The evolving roles of parents and children in making decisions related to research participation as children mature and the role of the IRB are the two main issues that are addressed in this article around which the recommendations are made. The document also presents guidance on a variety of paediatric-specific consent issues that arise frequently in the development of biorepositories.
Read the PubMed abstract


New Syndromes

Novel syndrome of developmental delay, microcephaly, epileptic seizures and facial dysmorphism due to DYRK1A mutations
The authors described two patients with DYRK1A mutations sharing many clinical features with previously reported cases. This syndrome may represent a recognizable phenotype including developmental delay or intellectual disability with behaviours suggesting autism spectrum disorder, microcephaly, epileptic seizures, and facial dysmorphism including ear anomalies (large ears, hypoplastic lobes), thin lips, short philtrum and frontal bossing.
Consult the Pubmed abstract

Eur J Med Genet. ; 58(3):168-74 ; March 2015
Autosomal dominant bleeding disorder caused by THBD mutation in two families
The authors described a family with an autosomal dominant disorder characterized by severe trauma- and surgery-related bleeding. The underlying genetic defect was identified as the THBD mutation. The same mutation has been recently reported in an unrelated British family. Patients had decreased expression of endothelium-bound thrombomodulin, but extremely elevated levels of soluble thrombomodulin in plasma, impairing the propagation phase of coagulation.
Consult the Pubmed abstract

Blood ; 125(9):1497-501 ; February 2015
Ocular coloboma, microcornea and cataracts due to mutations in MAB21L2
The authors reported on a family affected with dominant coloboma, microcornea, cataracts, and skeletal dysplasia. They identified a heterozygous mutation in MAB21L2.
Consult the Pubmed abstract

PLoS Genet. ; 11(2):e1005002 ; February 2015
Uncommon aniridia-like phenotype in two children
The authors reported on one child with a deletion and another with a duplication involving 6p25, causing an uncommon aniridia-like phenotype. Although these patients had no iris, they did not have other findings of aniridia except glaucoma.
Consult the Pubmed abstract

Am J Med Genet A. ; 167(3):524-8 ; March 2015

New Genes

Association of familial vascular leukoencephalopathy with COL4A2 variation
Consult the Pubmed abstract
To read more about "Familial vascular leukoencephalopathy"

Neurology ; 84(9):918-26 ; March 2015
Hereditary spastic paraplegia due to a homozygous mutation in IBA57
Consult the Pubmed abstract
Neurology ; 84(7):659-67 ; February 2015
Acute myeloid leukemia defined by distinct somatic mutations in SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, or STAG2
Consult the Pubmed abstract
To read more about "Acute myeloid leukemia"

Blood ; 125(9):1367-76 ; February 2015
Amyotrophic lateral sclerosis-parkinsonism-dementia complex linked to homozygous PINK1, heterozygous DCTN1, FUS and HTT pathogenic mutations
Consult the Pubmed abstract
To read more about "Amyotrophic lateral sclerosis-parkinsonism-dementia complex"

Ann Neurol. ; 77(3):458-68 ; March 2015
Coats plus syndrome and dextrocardia might be associated with CTC1, HES7 and TEK mutations in an Indian family
Consult the abstract
To read more about "Coats plus syndrome"
To read more about "Dextrocardia"

BMC Medical Genetics ; [Epub ahead of print] ; February 2015

Research in Action

Clinical Research
Systemic-onset juvenile idiopathic arthritis: catch-up growth during tocilizumab therapy
Consult the Pubmed abstract
Consult this study on Orphanet

To read more about "Systemic-onset juvenile idiopathic arthritis"

Arthritis Rheumatol. ; 67(3):840-8 ; March 2015
Congenital cytomegalovirus disease: valganciclovir seems to modestly improve hearing and developmental outcomes in the long term
Consult the Pubmed abstract
N Engl J Med. ; 372(10):933-43 ; March 2015
Glycogen storage disease due to glucose-6-phosphatase deficiency: new uncooked waxy maze starch leads to significant reduction in insulin release and reduced starch use
Consult the Pubmed abstract
To read more about "Glycogen storage disease due to glucose-6-phosphatase deficiency"

Orphanet J Rare Dis. ; 10(1):18 ; February 2015
Monogenic dystonia: pallidal neurostimulation improves the disease
Consult the Pubmed abstract
To read more about "Primary dystonia, DYT6 type"
To read more about "Early-onset generalized limb-onset dystonia"

Neurology ; 84(9):895-903 ; March 2015
Primary central nervous system lymphoma: mitigated results with high-dose chemotherapy with autologous stem-cell transplant
Consult the Pubmed abstract
To read more about "Primary central nervous system lymphoma"

Blood ; 125(9):1403-10 ; February 2015
Multiple myeloma: pomalidomide plus low-dose dexamethasone prolongs overall survival and is well tolerated
Consult the Pubmed abstract
To read more about "Multiple myeloma"

Blood ; 125(9):1411-7 ; February 2015
Infantile hemangioma: efficiency of the propranolol treatment
Consult the Pubmed abstract
N Engl J Med. ; 372(8):735-46 ; February 2015
Soft-tissue sarcoma: it is not recommended to stop trabectedine treatment in patients with advanced sarcoma and who have not progressed
Consult the Pubmed abstract
Lancet Oncol. ; 16(3):312-9 ; March 2015
Congenital fibrosis of extraocular muscles: expanding the phenotypic spectrum
Consult the Pubmed abstract
To read more about "Congenital fibrosis of extraocular muscles"

J Clin Endocrinol Metab. ; 100(3):E473-7 ; March 2015
Autosomal dominant childhood-onset proximal spinal muscular atrophy: expanding the phenotypic spectrum with the inclusion of generalized arthrogryposis
Consult the Pubmed abstract
To read more about "Autosomal dominant childhood-onset proximal spinal muscular atrophy"

Neurology ; 84(7):668-79 ; February 2015
Therapeutic Approaches

Niemann-Pick disease type C: intracisternal cyclodextrin prevents cerebellar dysfunction and Purkinje cell death in a cat model
Consult the Pubmed abstract
To read more about "Niemann-Pick disease type C"

Sci Transl Med. ; 7(276):276ra26 ; February 2015
Hemophilia B: liver-directed gene therapy in a dog model is well tolerated and provides a stable long-term production of coagulation factor IX
Consult the Pubmed abstract
To read more about "Hemophilia B"

Sci Transl Med. ; 7(277):277ra28 ; March 2015
MCC950, a small-molecule inhibitor of NLRP3, rescued neonatal lethality in a mouse model of CAPS and was active in ex vivo samples from individuals with Muckle–Wells syndrome
Consult the Pubmed abstract
To read more about "Cryopyrin-associated periodic syndrome"
To read more about "Muckle-Wells syndrome"

Nat Med. ; 21(3):248-55 ; March 2015
Duchenne muscular dystrophy: functional correction in mouse models using exon-skipping tricyclo-DNA oligomers
Consult the Pubmed abstract
To read more about "Duchenne muscular dystrophy"

Nat Med. ; 21(3):270-5 ; March 2015
Philadelphia chromosome-positive acute lymphoblastic leukemia: janus kinase inhibition by ruxolitinib extends dasatinib- and dexamethasone-induced remissions in a mouse model
Consult the Pubmed abstract
Blood ; 125(9):1444-51 ; February 2015
Diagnostic Approaches

Differential diagnosis of Mendelian and mitochondrial disorders in patients with suspected multiple sclerosis
Consult the Pubmed abstract
Brain ; 138(Pt 3):517-539 ; March 2015

Patient Management and Therapy
Progress and challenges of targeted delivery of siRNA therapeutics
Consult the Pubmed abstract
J Control Release. ; 203C:1-15 ; February 2015
Tolerance and efficacy of off-label anti-interleukin-1 treatments in France
Consult the Pubmed abstract
Orphanet J Rare Dis. ; 10(1):19 ; February 2015
Leukodystrophies and leukoencephalopathies: review on therapies
Consult the Pubmed abstract
Mol Genet Metab. ; [Epub ahead of print] ; February 2015
Autoimmune and systemic inflammatory diseases: management of fertility, pregnancy and lactation in women
Consult the Pubmed abstract
Arthritis Care Res (Hoboken). ; 67(3):313-25 ; March 2015
Progressive supranuclear palsy: review on pathophysiology, genetics, clinical features, diagnosis and therapeutic trials
Consult the abstract
To read more about "Progressive supranuclear palsy"

Expert Opinion on Orphan Drugs ; 3(3):253-265 ; March 2015
Paediatric inherited thrombophilia: review on manifestations and clinical impact
Consult the Pubmed abstract
Blood ; 125(7):1073-1077 ; February 2015
Mucopolysaccharidosis type 1: review on diagnosis, classification and treatment
Consult the abstract
To read more about "Mucopolysaccharidosis type 1"

Expert Opinion on Orphan Drugs ; 3(3):307-320 ; March 2015
Neurofibromatosis type 2: review on pathogenesis and management
Consult the abstract
To read more about "Neurofibromatosis type 2"

Expert Opinion on Orphan Drugs ; 3(3):281-292 ; March 2015
Cryptococcosis: review on management
Consult the Pubmed abstract
To read more about "Cryptococcosis"

Lancet Infect Dis. ; 15(3):348-355 ; March 2015
Neuroendocrine carcinoma of the bladder: a review
Consult the abstract
To read more about "Small cell carcinoma of the bladder"

International Cancer Conference Journal ; [Epub ahead of print] ; February 2015
Spondyloepiphyseal dysplasia congenita: study of clinical and radiological features in a cohort of 93 patients with a COL2A1 mutation
Consult the Pubmed abstract
To read more about "Spondyloepiphyseal dysplasia congenita"

Am J Med Genet A. ; 167(3):461-75 ; March 2015

Orphan Drugs
Glybera gene therapy set at €1-million in Germany
Glybera (alipogen tiparvovec) is the first gene therapy to be approved by Europe and the United States to go on sale. Last year, Glybera presented their pricing dossier to Germany, charging €1 million per treatment, which has been recently been approved. Some critics believe that this price is exorbitant and might set a benchmark for similar therapies and sets a question as to how governments and private insurers will pay for this treatment. However, others believe that since this medication is a one-time only treatment, the company should be allowed to make its profits warranting a high one-time only price.
Read More

Orphan medicinal product regulation for haemophilia criticised due to the paediatric clinical trial requirement
An opinion piece published in Haemophilia states that when it comes to treating haemophilia, medications do not need orphan drug designation to be profitable. According to the authors current global market for haemophilia products is worth in excess of US $ 7 billion. According to the author, the orphan drug designation and marketing exclusivity should be reserved only for very rare bleeding disorders such as FII, FV, FX and FXIII deficiencies, while providing new haemophilia treatment market exclusivity can “set a dangerous precedent and gravely damage patients’ rights to access”. This is mainly because the author perceives the requirement of paediatric clinical trials and sequential testing of some haemophilia drugs before approval for adults as unnecessary. The author also states that the “new longer acting products are not similar and that each protein modification should be treated as distinct and therefore be granted marketing authorisation”, without the paediatric testing requirement.
Access the article

NICE recommends Gazyvaro for reimbursement
NICE has issued a final appraisal for Gazyvaro in combination with chlorambucil chemotherapy for the treatment of adults with chronic lymphotic leukaemia (CLL). Gazyvaro (obinutuzumab) will be a treatment option for adults who are previously untreated or have coexisting medical conditions that mean they are unsuitable for full dose fludarabine or bendamustine based therapy.
For further information

Regulatory News
FDA approves unituxin for the treatment of rare childhood cancer
Unituxin (dinutuximab) by United Therapeutics has become the first ever therapy approved by the United States Food and Drug Association (US FDA) for neuroblastoma, a rare form of cancer that most commonly occurs in young children. Unituxin is an antiGD2 antibody that binds to a glycolipid antigen on the surface of neuroblastoma cells. It has been approved for use in combination with immune stimulating drugs in high risk patients who have responded at least partially to first line therapy. The safety and efficacy of this drug was tested in a 226 patient study whose tumours shrank after surgery and multidrug chemotherapy, along with radiotherapy and a bone marrow transplant.

To encourage companies to pursue development of therapeutics for rare paediatric disease, the FDA has conferred United Therapeutics with a rare paediatric disease priority review voucher. This voucher can be used by the manufacturer for a subsequent drug application that would not otherwise qualify for priority review.
Read the FDA press release

Australia: postmarket review of the Life Saving Drugs Programme
The Australian government provides subsidised access, for eligible patients, to expensive life saving drugs for certain rare diseases through the Life Saving Drugs Programme (LSDP). In order to assess the efficiency and to decide on the future direction of LSDP, the Australian Department of Health announced the post-market review of the Life Saving Drugs Programme (LSDP Review), last year.

According to the Department of Health, the Review will examine issues of “access and equity, value for money and the future administration of the programme”. The public consultation on the Life Saving Drugs Programme (LSDP) part of the review has been completed and all the submissions are now available on the Pharmaceutical Benefits Scheme (PBS) website. The review will be complete by the end of April at which time PBS will release the results and recommendations.
Read the public comments on the PBS website

Still no decision to fund Orfadin for the treatment of tyrosinaemia type 1
Also in Australia, following a stakeholder meeting held to consider the PBS funding of Orfadin (nitisinone) for the treatment of tyrosinaemia type 1 (HT-1), the Pharmaceutical Benefits Advisory Committee (PBAC) deferred making a recommendation, for the second time, regarding the Authority listing under Section 100, where the Australian government reimburses pharmacies and hospital authorities. The PBAC have asked for further clarity around current and future screening practices for detecting HT-1 and the potential impact on survival advantage and adverse effects of treatment.
Read the outcome statement

Political and Scientific News
The challenges and benefits of enzyme replacement therapy
A review published in Expert Opinion on Orphan Drugs highlights the potential reasons why enzyme replacement therapies (ERT) has not been as universally successful as hoped. ERT has been successfully introduced for patients with Gaucher disease type 1 (GD type 1), which led to this treatment principle being taken into consideration for other lysosomal storage disorders (LSDs) as well. However, repeating this spectacular success in the mucopolysaccharidoses and Fabry or Pompe disease proved to be impossible.

According to the authors the therapeutic success of imiglucerase in GD type 1 was due to a combination of several factors, such as a “largely reversible disease, readily monitored response to treatment, and specific targeting of the drug to the restricted population of cells of interest”. However, in other diseases the success is limited due to lack of beneficial effects on all aspects of a disorder to the same degree, even with an early introduction of treatment. Delivering therapeutic levels of lysosomal enzymes to cross the blood-brain barrier, affect on dysostosis multiplex, joint disease or cardiac valve disease has been challenging. However, despite these drawbacks, the authors maintain that availability of ERT, has changed the nature of LSDs, as it has provided relevant knowledge on the clinical features, course of diseases, pathophysiology as well as research on genotype phenotype correlations.
Access the article

Scientific framework for using the accelerated approval pathway and for qualifying biomarkers as primary endpoints to develop orphan drugs
The accelerated approval (AA) pathway is able to serve a vital role for the development of treatments for diseases with high unmet medical needs. An article published in the Orphanet Journal of Rare Diseases describes a scientific framework for assessing biomarker endpoints with defined sets of supporting data more structured approach which will enhance the development of novel orphan drugs for rare diseases currently without adequate treatment and is based on the opinions of experts in drug development and rare disease patient groups. The authors suggest the following recommendations for the development of orphan drugs using the Accelerated Approval pathway and for qualifying biomarkers as primary endpoints:

-Establishing Regulatory Rationale for Accelerated Approval Access in Rare Disease Programs
-Implementing a Biomarker Qualification Request Process
-A Proposed Scientific Framework for Qualifying Biomarkers as Surrogate Primary Endpoints

Although this article mainly describes the examples from the United States Food and Drug Administration (US FDA), they are relevant to sponsors applying for marketing authorisation to other world regions as well.
Read the open access article



NBIA Disorders Association Grant for Neurodegeneration with Brain Iron Accumulation (NBIA)
The purpose of the NBIA Disorders Association Research Grant Program is to encourage meritorious research studies designed to improve the diagnosis or treatment of NBIA. The research can be conducted in countries where adequate supervision of grant administration is possible. The NBIA Disorders Association is accepting applications for one-year grants for clinical and translational research studies related to the early detection, diagnosis, or treatment of patients with NBIA. Application Deadline: April 1, 2015
For further information

DEBRA International : Call for research proposals
DEBRA International is now inviting expressions of interest for funding support of clinical research and clinical trials targeting therapy development and symptom relief for epidermolysis bullosa (EB). There is a two stage application process, with a submission deadline for stage 1 proposals (expressions of interest) on 1 April 2015. Proposals are invited which make a breakthrough in developing therapies that address the underlying causes or the life limiting consequences of EB (e.g. EB related squamous cell carcinoma), or in developing symptom relief treatments that address clinical consequences of EB that impact upon quality of life.
For further information

The ECD Global Alliance is soliciting Letters of Intent for funding of research projects focused on the study of Erdheim-Chester Disease
All investigation proposals will be considered and all qualified and interested investigators are encouraged to submit. As appropriate, submitted studies should consider inclusion of the following: Collaboration among investigators from different institutions as well as translation of findings into the clinical setting.
Maximum Amount of Monies to be Awarded: Up to $100,000 USD (total)
Duration of Grant: 1 Year
LOI Deadline: April 2, 2015

For further information

The Ataxia of Charlevoix-Saguenay Foundation
The Ataxia of Charlevoix-Saguenay Foundation offers annual research fellowships that will lead to a treatment for autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). A maximum of $100,000 could be awarded for a period of one year and could be renewed for a second year by way of a new application. Application Deadline: May 22, 2015
For further information

AFM Telethon: Call for proposals
Several call for proposals are being made available by AFM Telethon. They have published a call for proposals for Spinal Muscular Atrophy and Collagen VI Call for Projects.
For further information


Courses & Educational Initiatives

Date: 1-5 June, 2015
Venue: Barcelona, Spain

ExPRESS 2015 is the name of the exciting new programme for the upcoming annual EURORDIS Summer School. ExPRESS, which stands for Expert Patients and Researchers EURORDIS Summer School, will gather for the first time both researchers and patient representatives who will be trained together. The trainers are from patient organisations, research institutes and the European Medicines Agency. The four-day training programme develops the capacity of patients' advocates to act as experts in regulatory processes and further their implication in medicines development and advocacy actions both at the national and European levels.
For further information contact Nancy Hamilton
Visit the EURORDIS website for more information.

3rd radiz Rare Diseases Summer School
Date: 1-3 July, 2015
Venue: Zurich, Switzerland

The 3rd radiz Rare Diseases Summer School will focus on a wide variety of subjects in the arena of rare diseases, from disease mechanisms and animal models, to improving diagnoses, to novel therapeutics. There will be lectures and workshops on drug development, model organisms, how to choose clinical endpoints, clinical trials, regulatory aspects, patient registries, patient initiated research, ethical considerations, as well as what rare diseases may tell us about common diseases. The summer school will contain lectures by national and international rare disease experts, workshops, and poster presentations by participants.
Visit the EURORDIS website for more information.

The 2nd Biennial Australian Rare Lung Disease Short Course
Date: 16-17 October, 2015
Venue: Sydney, Australia

The joint venture between Lung Foundation Australia and the Thoracic Society of Australia and New Zealand (TSANZ) will provide updates on the latest in research, diagnosis, therapy and care for Interstitial Lung Disease. The program boasts an exceptional selection of Australian specialists as well as keynote presentations from international speaker, Professor Kevin Flaherty (USA).
For further information or to register please visit: www.lungfoundation.com.au.

Courses offered by Recordati Rare Diseases Foundation
The Recordati Rare Diseases Foundation is offering five courses planned for next year. For further information, please contact Cecilia Kellquist, Coordinator and member of the board, ckellquist@rrd-foundation.org/www.rrd-foundation.org.
The changing spectrum of IMD: surviving longer and growing old with IMDs
Date: 21-23 May, 2015
Venue: Washington DC, US

Children’s Hospital of Pittsburgh, the Division of Medical Genetics and Children’s National, Department of Genetics and Metabolism.
Registration deadline: 8th April

Classification and diagnostic approach of IMD affecting the synthesis and remodelling of complex lipids
Date: 24-26 June 2015
Venue: Paris, France

in partnership with the Pitié-Salpêtrière Hospital Pierre et Marie Curie University Paris VI; the Academic Medical Center, University of Amsterdam and the University Children’s Hospital of Zurich.
Registration deadline: 13th May

Genetic congenital heart diseases
Date: 7-9 October 2015
Venue: Rome, Italy

in partnership with Bambino Gesù Children’s Hospital, Rome
Registration deadline: 27th August

Neurotransmitter focus course
Date: 9-10 November 2015
Venue: Venice, Italy

in partnership with University Hospital for Child and Adolescent Medicine of Heidelberg and University Hospital of Padua. Registration deadline: 26th September


What's on Where?

3rd Asia-Pacific Prader-Willi Syndrome Conference 2015: From Better Start to Better Living
Date: 11-12 April, 2015
Venue: Melbourne, Australia

The theme of this conference is “From better start to better living” and will provide an opportunity for scientists, professionals, parents and caregivers to join together, providing a forum to share expertise.
For further information

Genetic insider: 1st International congress on Clinical Genetics and Genetic Counselling
Date: 16-17 April, 2015
Venue: Seville, Spain

Genetic Insider The connection platform among European and American clinical professionals and industry, to promote the necessary partnership networks for rare diseases.
For further information

3Gb-TEST course on NGS: Next-generation sequencing in a diagnostic setting
Date: 20-23 April, 2015
Venue: Prague, Czech Republic

A 4-day course on Next Generation Sequencing in Prague - Czech Republic in the period of 20-23th April 2015. The focus of the course is on clinical diagnostics using exome/genome sequences, variant identification and analysis including afternoon practicals (limited places). The course will also include an evening symposium co-organised by Milan Macek; “Genotranslation: Interpretation of genome data in diagnostics”.
For further information

13th International Symposium on Mutation in the Genome: detection, genome sequencing & interpretation
Date: 27 APRIL, 2015
Venue: Leiden, Netherlands

The meeting aims to present the latest developments in the field, the best methodologies for scanning, sequencing, bioinformatic, analysis and functional testing.
For further information

2nd International GENCODYS Conference on Integrative Networks in Intellectual Disabilities
Date: 27-29 April, 2015
Venue: Crete, Greece

European funded research consortium GENCODYS exploits a multilevel approach to resolve the integrative networks in intellectual disabilities. The conference will bring together about 150 top researchers, medical doctors and patient representatives in the field of Cognitive Research and related activities.
Talks and submissions for talks have to be related to studies of cognitive dysfunction but can include other fields, namely genetics, cellular, molecular and physiological studies, genomics and epigenomics and bioinformatics.
For further information

6th International conferences on ectodermal dysplasia
Date: 27-30 May, 2015
Venue: Oslo, Norway

The conference will attract medical and dental clinicians and researchers from many countries in addition to patient organisation leaders from all over the world.
For further information

Trisomy 21 Research Society (T21RS) International Conference
Date: 4-6 June, 2015
Venue: Paris, France

T21RS promotes research on Down syndrome and stimulates collaboration between researchers worldwide. The first edition of the T21RS International Conference will be held at the site of the Hôpital de la Pitié-Salpêtrière in Paris. More details will be announced in due course.
For further information

The European Human Genetics Conference 2015
Date: 6-9 June, 2015
Venue: Scotland, United Kingdom

The European Human Genetics Conference is a forum for all workers in human and medical genetics to review advances and develop research collaborations.
For further information

34th Annual European Malignant Hyperthermia Group (EMHG) Meeting
Date: 11-13 June, 2015
Venue: Lille, France

The topics will cover all the fields of interest in malignant hyperthermia, such as invitrocontracturetesting, genetics, clinical and experimental issues, updates and forthcoming projects. The scientific program of the European Malignant Hyperthermia Group (EMHG) will be on state-of-the-art presentations in our field as well as new insights into basic science, clinical research and therapeutic interventions.
For further information

22nd International Meeting of the Pediatric Colorectal Club 2015
Date: 13-15 June, 2015
Venue: Milan, Italy

This meeting aims to provide up to date clinical and scientific information on all aspects of paediatric colorectal disease to practicing paediatric surgeons, nurses and parents’ Associations.
For further information

International Myotonic Dystrophy Consortium Meeting (IDMC)
Date: 8-12 June, 2015
Venue: Paris, France

This consortium will bring together not only scientists and clinicians but also family associations and patients.
For further information

Tourette Syndrome Congress 2015
Date: 24-26 June, 2015
Venue: London, UK

The 1st World Congress on Tourette Syndrome and Tic Disorders is designed for linicians, researchers , post-doctoral fellows, medical residents and allied healthcare professionslas with an interest in current research, diagnosis and treatment of these and related conditions.
For further information

7th International Conference on Children’s Bone Health
Date: 27-30 June, 2015
Venue: Salzburg, Austria

The International Conference on Children’s Bone Health (ICCBH) meetings provide an international forum for the presentation and discussion of current basic and clinical science in the field of bone metabolism and bone mass in children, adolescents and young adults.
The call for abstracts opens in September 2014.
Abstract deadline: 6 February 2015.
For further information

The First Russian Congenital Aniridia Conference
Date: 3-4 July, 2015
Venue: Salzburg, Austria

The conference will aim at sharing knowledge and experience about Congenital Aniridia by increasing the dialogue between patients and doctors about the problems of congenital aniridia.
For further information

10th European Cytogenetics Conference
Date: 4-7 July, 2015
Venue: Strasbourg, France

The 10th European Cytogenetics Conference allows all cytogeneticists from Europe and further afield to come together to hear about and discuss the most exciting developments ranging from applications in prenatal or cancer diagnosis to chromosome biology in epigenetics and evolution.
For further information

10th International Conference: One Carbon Metabolism, vitamins B and Homocysteine
Date: 7-11 July, 2015
Venue: Nancy, France

The conference will deal with a very interdisciplinary program joining leading scientists from biochemical, experimental and clinical medical area. It will cover the most advanced research on One Carbon Metabolism, Homocysteine and related coenzymes and vitamins, including folate, vitamin B12 (cobalamins), vitamin B6 (pyridoxine) and choline in the fields of biochemistry, metabolism, nutrition, epidemiology and experimental and clinical medicine.
For further information

4th International RASopathies Symposium
Date: 17-19 July, 2015
Venue: Washington, US

This conference will bring together caregivers, clinicians, patients, researchers and pharmas with an aim to expedite treatments and cures for the RASopathies.
For further information

Glycoproteinoses: Fourth International Conference on Advances in Pathogenesis and Therapy
Date: 23-26 July, 2015
Venue: Missoouri, US

The Fourth International Conference on the Glycoproteinoses will bring together leading investigators from around the world to discuss the latest advances in understanding the pathophysiology of these rare disorders and the status of the development of new therapies.
For further information

SSIEM Official Satellite Symposia Second World Conference on Congenital Disorders of Glycosylation (CDG)
Date: 28-30 August, 2015
Venue: Lyon, France

This conference aims to raise awareness about Congenital Disorders of Glycosylation (CDG) around the world and to foster an exceptional collaborative model involving patients, family members, researchers and physicians.
For further information

26th European Dysmorphology Meeting
Date: 9-10 September, 2015
Venue: Le Bischenberg, France

The principal aim of this meeting has been to bring young clinical geneticists and trained dysmorphologists together to share their professional experiences and present their clinical challenges. EuroDysmorpho is open to any presentation in the field of human development.
For further information

Tyrosinemia 2015
Date: 24-26 September, 2015
Venue: Quebec, Canada

The Quebec parent association (GAETQ) is organizing an international conference on Tyrosinemia. The objective is to share and update our knowledge regarding this disease and its impacts on the medical world. Tyrosinemia was identified fifty years ago and used to greatly diminish the life expectancy of children affected. Now the disease is well controlled, thanks to NTBC.
For further information

The PANDAS 2015
Date: 26 September, 2015
Venue: Lake Como, Italy

Presentations of the latest scientific advances in the diagnosis and treament of PANS/PANDAS shall include topics touching immunology, rheumatology, neurology, child psychiatry, psychology and more.
For further information

8 International Congress of Familial Mediterranean Fever and Systemic Autoinflammatory Diseases
Date: 30 September – 3 October, 2015
Venue: Dresden, Germany

This meeting will offer numerous opportunities to convene with experts on FMF and other auto-inflammatory diseases. This meeting hopes to welcome more than 400 participants from all over the world to discuss the latest scientific and clinical developments, including new treatment options.
For further information

4th Congress on Mitochondrial Medicine
Date: 9-10 July, 2015
Venue: Salzburg, Austria

The meeting addresses the importance of mitochondrial pathology in neurology, pediatrics and beyond. An overview on the newest research developments and important clinical aspects will be provided. Deadline for the submission of scientific abstracts is May 15th and for early registration is June 1st.
For further information

First European Congress on Hereditary ATTR amyloidosis ECATTR
Date: 2-3 November, 2015
Venue: Paris, France

The European Congress for HATTR will allow the meeting of the specialists of all European countries and the sharing of experience. The effort will be to further improve the early diagnosis of sporadic cases and genetic carriers, to review anti-amyloid treatments and clinical trials, to improve genetic counselling.
For further information

2nd International Primary Immunodeficiencies Congress (IPIC)
Date: 5-6 November, 2015
Venue: Budapest, Hungary

The International Patient Organisation for Primary Immunodeficiencies (IPOPI) announces the Second International Primary Immunodeficiencies Congress (IPIC). This event will build on the successful outcomes of the first IPIC, attended by 400 participants. The congress will consist of a two-day programme and is open to all stakeholders with an interest in clinical management of primary immunodeficiencies (PIDs).
For further information

13th International Congress of Human Genetics (ICHG) 2016
Date: 3-7 April, 2016
Venue: Kyoto, Japan

Hosted by the East-Asian Union of Human Genetic Societies (EAUHGS) and the Japan Society of Human Genetics, the 13th ICHG will focus on progress in genome analysis technologies and big data in order to explore disease mechanisms and treatment opportunities.
Registrations open in 2015.
For further information

ESID European Society for Immunodeficiencies: Biennial meeting
Date: 21-24 September, 2016
Venue: Barcelona, Spain

Sessions at this meeting will be devoted to understanding primary immunodeficiencies and their clinical aspects.
For further information


Commercial events

Pharma Pricing and Market Access Congress 2015
Date: 24-26 February, 2015
Venue: London, UK

The conference provides information on the latest policies affecting market access from payers, HTA authorities and leading industry experts.
For further information

World Orphan Drug Congress USA 2015
Date: 3-7 April, 2015
Venue: Maryland, USA

World Orphan Drug Congress is the premier commercial event for the global rare disease industry. Differentiate yourself from the competition by discovering the latest strategies for sustainability, pricing and reimbursement, commercialization and global market access.
For further information

10th annual World Stem Cells & Regenerative Medicine Congress
Date: 20-22 May, 2015
Venue: Maryland, USA

Discover and understand how industry leaders view the clinical and commercial futures of stem cells and regenerative medicine and the effect it will have on business.
For further information

Pan-Omics Summit
Date: 21-22 May, 2015
Venue: Massachusetts , US

Representatives from big pharma, academic institutions, and government research labs will present data on advances in new technology and case studies on therapeutic targets, molecular diagnostics, and integration of complex data.
For further information

2nd Metabolomics - Advances & Applications in Human Disease Conference
Date: May 21-22, 2015
Venue: Massachusetts, US

This event will present new research and offers networking opportunities with the researchers and scientists who are working on developing clinical assays, connecting the metabolome and the genome, and establishing common quality standards for experimental data.
For further information

World Orphan Drug Congress Asia 2015
Date: 3-4 June, 2015
Venue: Singapore

This event will bring together specialised biotechs/pharmas, government, payers, investors & patient groups in one platform, this event offers a unique opportunity to increase brand visibility amongst the rare disease industry in Asia.
For further information

Orphan Drugs Summit 2015
Date: 17-18 September, 2015
Venue: Copenhagen, Denmark

This conference will bring together different groups of stakeholders on specifically selected topics to help them build relationships and reach their goals.


OrphaNews, The Newsletter of the Rare Diseases Community.
OrphaNews is supported by the European Commission's DG SANCO (EUCERD Joint Action N° 2011-22-01)
and the French Muscular Dystrophy Association (AFM)
Editor-in-chief: Ségolène Aymé
Editor: Divya Unni
Editors for Scientific Content: Sophie Höhn
Contact Us
Editorial Board: Ségolène Aymé, Paul Boom, Anna Bucsics, Kate Bushby, Lorenzo Dagna, Adam Heathfield, Lilian Lau, Yann Le Cam, Jordi Llinares-Garcia, Antonia Mills, Antoni Monserrat, Ana Rath, Charlotte Rodwell, Gerhard Steffes, Till Voigtländer, Jaroslaw Waligora

Orphanet Partner Country Representatives: Kristine Hovhannesyan (Armenia), Hugh Dawkins (Australia), Till Voigtlander (Austria), Rumen Stefanov (Bulgaria), Ana Stavljenic-Rukavina (Croatia), Violetta Anastasiadou (Cyprus), Milan Macek (Czech Republic), John Rosendahl Ostergaard (Denmark), Vallo Tillmann (Estonia), Riitta Salonen (Finland), Joerg Schmidtke (Germany), Helen Michelakakis (Greece), Eileen Treacy (Ireland), Annick Raas-Rothschild (Israel), Bruno Dallapiccola (Italy), Tomoko Kodama (Japan), Jana Lepiksone (Latvia), André Mégarbané (Lebanon), Vaidutis Kucinskas (Lithuania), Yolande Wagener (Luxembourg), Abdelaziz Sefiani (Morocco), Gert-Jan van Ommen (Netherlands), Stein Are Aksnes (Norway), Malgorzata Krajewska-Walasek (Poland), Jorge Sequeiros (Portugal), Cristina Rusu (Romania), Dragica Radojkovic (Serbia), Laszlo Kovacs (Slovakia), Borut Peterlin (Slovenia), Francesc Palau (Spain), Désirée Gavhed (Sweden), Loredana D'Amato Sizonenko (Switzerland), Ugur Ozbek (Turkey), Dian Donnai (UK)
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