As you will read in this issue of OrphaNews Europe, the milieu of scientific journal publishing has been in the news this month. The European Commission is taking a look at the subject with an eye to improving access to publicly funded research. In the US, a study reveals that the country's published stem cell research is losing its footing, while China bursts forth with 34 scientific publications available in English for the first time. Meanwhile, orphan disease and treatment research has finally found a home with the debut of OJRD – the Orphanet Journal of Rare Diseases. Two months after the official launch of the journal, over a dozen articles have already been brought to publication - and they have been accessed by some 4000 readers to date. Review articles on celiac disease, systemic lupus erythematosus, naxos disease, and premature ovarian failure have especially attracted interest.
At OrphaNews Europe we are looking at our own publication as the date of our one-year anniversary draws near. We, too, are interested in producing the best publication possible and doing all we can to meet the needs of our readers. In order to fulfil this important goal, we ask you, our valued readers, to take a few minutes to complete our survey questions and return your answers to us. A summary of the results will appear in the anniversary edition of OrphaNews Europe.
Editorial
Spotlight on...
Interview
Can chemical libraries help advance rare disease academic research?
Prestwick Chemical Inc. (PCI), established in 1999, provides innovative libraries to pharmaceutical and biotechnology companies, as well as academic research laboratories. Designed to help scientists discover medicinal products, PCI offers a broad range of expertise in medicinal chemistry, particularly in hit and lead optimisation. Such libraries can be a useful tool in facilitating academic research. OrphaNews Europe interviewed sales manager Dr. Marie-Louise Jung to learn more about the possible relevance of chemical libraries to rare disease academic research:
OrphaNews Europe: What PCI products and/or services are of particular interest to rare disease treatment development?
MLJ: The Prestwick Chemical Library, composed of 1120 molecules which are mainly drugs out of patent, is a compound collection dedicated to screening for all laboratories searching for new and safe hits. This library can be recommended particularly for rare disease research, as it allows a fast lead development, the selection of molecules being known for their bioavailability and safety in humans. Furthermore, Prestwick Chemical offers optimisation of the lead into a drug candidate in form of a contract research service.
OrphaNews Europe: What are the benefits to researchers in opting to work with marketed drugs and products?
MLJ: If a compound hits with sufficient potency, the chances are high that it could rapidly be tested in patients, and a use-patent may be possible.
If a compound hits with insufficient potency, optimised analogues can be synthesized. The chances that these analogues will be good candidate drugs for further development are much greater than if the initial lead is toxic or not bioavailable.
OrphaNews Europe: What kinds of rare disease research has PCI been involved in? Have you worked with rare disease research teams in Europe?
MLJ: We have been involved with an American team on a neuro-degenerative disease, but have so far been requested to maintain strict confidentiality. We have also collaborated with an academic team in Lyon on Duchenne’s muscular dystrophy.
A rare disease expert comments on molecule libraries
Dr. Pascale Borensztein, General Secretary of the GIS-Institut des Maladies rares (Rare Diseases Institute) is responsible for coordinating rare disease research and funding opportunities for academia. OrphaNews Europe asked Dr. Borensztein to comment on the role molecule libraries can play in facilitating academic research:
The possibility to screen thousands of molecules on a specific cellular target may help to explore cellular function and to find new drug targets which could then move into the drug-development pipeline. One difficulty is to develop an adequate biological assay, another is to validate a match between a chemical and its target, and further develop the chemical. The more the library contains known products, which have already been developed and tested for bioavailability and toxicity, the more time the researcher can potentially save. Indeed such libraries could potentially allow the scientist to eliminate certain steps of development.
In order to provide new tools for therapeutic research for rare diseases, one hypothesis would be to make interesting chemical libraries available for research projects and teams.
EU Policy News
DG SANCO
EU health programme undergoes external evaluation
As was specified during its conception, the Health and Consumer Protection Directorate General (DG Sanco) Public Health Programme will be subjected to an external evaluation in 2006 in order to obtain “independent and evidence-based” data concerning the accomplishments of the programme from 2003–2005, including the initiatives and efforts in the field of rare disease research, information, and treatments. The evaluation will aim to assess what impact the programme has made on EU health, how efficiently resources have been employed in terms of meeting the objectives of the programme, and how consistent and complementary the health programme is compared with other European Commission initiatives and programmes. An inception report has been made available, detailing the specific areas the evaluation will investigate and the manner in which the evaluation will proceed. The Rare Diseases Task Force and Orphanet are amongst the projects chosen for interview as part of the appraisal process. The evaluation is due to be completed by year’s end. The results will be distributed to the European Parliament, the Council, the Economic and Social Committee and the Committee of the Regions, and will be available on the DG Sanco Public Health website.
DG Sanco rare disease web pages now available in German
The recently revamped rare diseases website section of Health and Consumer Protection Directorate General (DG Sanco) is now available in German, in addition to English, French, and Spanish. As was reported in the April edition of OrphaNews Europe, the updated pages detail the efforts of the European Union in the framework of different EU rare disease projects.
DG Research
European Commission studies scientific publication system in Europe
The European Commission has published a study examining the scientific publication system in Europe, making several recommendations designed to improve access to research, specifically calling for guaranteed immediate and long-term public access to publicly-funded research. Acknowledging that there is little public funding available for scientific publication, the report, produced by a panel of experts, seeks to assure an adequate system that rapidly disseminates information to a wide audience. Considering the large amounts of public funds invested in research, the study looks closely at the changing landscape of scientific publishing, and especially the potential of the growing internet-based online publication market, as a means to improving access. Recommendations include fund allocations providing for the costs of the author-pay open-access journal model, tax refunds for electronic journal publishers, and the establishment of a European-level non-profit research archive. The report examines the current condition of print journalism, which has been plagued by rising production prices and falling subscription numbers for the past thirty years. The report also looks at the climate of the electronic publication market, recommending a “level-playing field” that permits fair competition. The implications of the study are especially meaningful for rare disease researchers, for whom heightening public awareness remains a principal goal. Interested parties are invited to contribute their responses to the study by 1 June. A conference and debate on the subject are being planned for the autumn.
EMEA
European-wide database in the works
The BMJ reported in its 15 April issue that the European Medicines Agency is devising a pan-European drug database that would permit physicians and patients to have ready access to information concerning medicine products. The free-access database, dubbed Eudrapharm, is part of an effort to augment transparency following European legislation coming into effect last October. The database system would also allow physicians to immediately report any adverse effects to both manufacturers and regulators. A complementary EMEA tool, EudraVigilance, is designed to permit drug companies to report adverse reactions to national regulators online. The two tools are expected to eventually merge, yielding a comprehensive database, to which different stakeholders will be granted varied levels of access. A preliminary version of Eudrapharm is due out later this year. This could be a highly useful tool for physicians treating rare diseases for which therapeutic methods are not commonly known.
EMEA recruiting to fulfil tasks created by new paediatric regulation
The EMEA has posted vacancy notices for the following positions, created in part by new paediatric regulation:
Applications must be postmarked no later than 19 May, 2006. Full job descriptions and general application conditions are available.
National & International Policy Developments
Other European news
Rare diseases awareness day a success
As was reported in the 16 March issue of OrphaNews Europe, the German Congenital Immune Deficiency Self-Help group (Deutsche Selbsthilfe Angeborene Immundefekte or DSAI ), a member of patient organisation network Alliance of Chronic Rare Diseases (Allianz Chronischer Seltener Erkrankungen), launched a campaign in early April to inform politicians and the public of the issues surrounding rare diseases, particularly primary immune deficiency, and to encourage early diagnosis. The official launch was attended by high-ranking representatives from both the upper house of the German parliament (Bundesrat) and the German parliament (Bundestag), as well as the European Commission and members of the healthcare system. Results of the event include a demand for nation-wide provisions with special clinics and research centres; a call for immediate action on the part of politicians to improve the situation for patients; further education and training for practicing physicians to improve the diagnosis rate of rare diseases; strengthening the weight of immunology in medical faculties; and compulsory inclusion of rare disease treatment costs in health insurance company reimbursement policies. The event marks an important first step towards achieving these political objectives. The general consensus amongst the speakers concerning the urgency of required action is significant for the development of the campaign. The diagnosis and treatment of rare diseases need to be re-evaluated accordingly.
International policy
Electronic format required for orphan product designation requests
As of 1 April 2006, the US Office of Orphan Products Development will accept orphan-drug and humanitarian use device designation requests and related submissions in electronic format only. The Food and Drug Administration (FDA) has created a draft guidance document for electronic submission of designation requests entitled, Providing Regulatory Submissions in Electronic Format—Orphan-Drug and Humanitarian Use Device Designation Requests and Related Submissions. The FDA is accepting comments on the draft guidance from interested parties until 30 May, 2006.
US releases final report on genetic testing coverage and reimbursement
The United State’s Health and Human Services Secretary's Advisory Committee on Genetics, Health and Society (SACGHS) has released its final report entitled, Coverage and Reimbursement of Genetic Tests and Services. The report documents current policies concerning coverage and reimbursement, investigates patient access to and utilisation of genetic testing services and puts forward nine recommendations for improving the present system in both the public and private sectors. In terms of “experimental” rare disease genetic testing, which is more likely to be excluded from coverage, the report discusses the difficulties inherent in determining when genetic tests have evolved from the research phase to clinical use: “Establishing clinical validity and amassing sufficient data to achieve statistically significant results that satisfy evidence standards are especially difficult for rare diseases due to their low prevalence. In addition, scientific interest in any given rare disease also is a factor affecting data collection (and access to research testing). A specific rare disease may be studied by only one investigator in the country or world. Insufficient funding for the study of rare diseases also can impede the amassing of adequate data.” Thus, the Committee recommends convening a task group to develop guidelines for coverage decision-making, taking into account rare disease factors, amongst other issues. The task group should also assess existing evidence for specific genetic tests in terms of type, quality, and quantity, in order to determine whether the evidence is sufficient to establish a test’s analytical validity, clinical validity, and clinical utility. The group should identify any evidentiary gaps.
US industry and government to share treatment safety predictive methods
The US Food and Drug Administration (FDA) and the Critical Path Institute (C-Path), an independent non-profit research institution established in 2005 to improve and accelerate medical product development, have announced an unprecedented collaboration between several leading US pharmaceutical companies and C-Path in order to share internally-developed laboratory methods for predicting the safety of new treatments before being tested on humans. The FDA will participate in an advisory capacity. The Predictive Safety Testing Consortium, a public-private partnership, is designed to enable industry to pool resources and knowledge and to test and validate each others’ methods, which can then be collected and summarised by C-Path for submission to the FDA for the creation of agency-issued guidelines concerning the tests to be used in the drug development process. Ultimately, the effort should result in faster timeframes with more certainty and lower costs for drug development.
Other international news
New report looks at rare disease treatments in the US
The Pharmaceutical Research and Manufacturers of America (PhRMA), along with the National Organization for Rare Disorders (Nord) and Genetic Alliance, have published a study detailing the advances in US rare disease treatment. A decade of innovation states that over 160 drugs were approved in the US for rare disease treatment in the last decade (1995 –2005) versus 108 a decade earlier and less than 10 in the 1970s. The report highlights some of the treatments that have allowed patients to lead very different lives, reminding the reader that 85% - 90% of over 6000 rare diseases affecting some 25 million Americans are serious or life-threatening.
Are US stem cell policies impacting the amount of published research?
A study by a fellow at the Stanford University Center for Biomedical Ethics finds that US stem cell researchers are publishing less work proportionately, a likely reflection of US federal policies and funding restrictions. Although the total amount of published human embryonic stem cell research has increased – nearly tripling in 2003 and 2004 - published US research dropped from one-third of the total in 2003 to about one-fourth in 2004. As the biotechnology industry relies on new research to remain competitive, the decline is causing concern. In addition, the authors of the study point out that both American industry and patients may be placed at a disadvantage as stem cell discoveries become therapeutically useful. The findings are published in the April issue of Nature Biotechnology.
State seeks to lift restrictions on federal funding to small biotech firms
Massachusetts state officials and biotech leaders are campaigning to lift current restrictions that disqualify many small biotech firms from receiving government funding. Current law excludes companies receiving 51% or more of their funding from venture capitalist sources from receiving Small Business Innovation Research grants. According to industry analysts, the consequence is that some of the most promising innovations are ineligible for federal funding. Drugs, vaccines, diagnostics and devices for a “whole host” of rare diseases figure amongst the projects of small US biotech companies, according to a letter sent to congressional leaders by a coalition of more than 60 groups, including patient organisations.
Elsevier makes 34 Chinese science publications available in English
For the first time, research from 34 Chinese science journals is being translated into English. Elsevier, a major academic publisher, will furnish free-access to the English-language journals throughout 2006, after which they will be available by subscription. Subject areas include general medicine, including the Journal of the Chinese Medical Association, as well as genetics, genomics, proteomics and bioinformatics, nephrology, and obstetrics and gynaecology. A study by the Chinese Academy of Sciences acknowledges that although China publishes a large quantity of scientific papers (only five countries published more in 2003), the research is often not considered highly original, and thus is not frequently cited in later studies.
Second-order peer review system tested for journal articles
Other recent recommendations involving scientific publication come from authors published in the 19 April issue of JAMA, who created a second-order peer review system for journal articles in order to determine which articles are most relevant in specific clinical areas. Following their study involving over 110 clinical journals reviewed for relevance and newsworthiness by more than 2000 physicians recruited worldwide, the authors conclude that post-publication peer review differentiating articles according to specific clinical disciplines is feasible and useful.
Research in Action
New diseases & syndromes
New genes
New rare disease genes published on PubMed
Mutations in different components of FGF signaling in LADD syndrome
LADD syndrome is caused by FGF10 mutations
Recessive symptomatic focal epilepsy and mutant contactin-associated protein-like 2
Nat Genet ; 452-457 ; April 2006
Nat Genet ; 414-417 ; April 2006
Clinical Genetics ; 349-354 ; April 2006
N Engl J Med ; 1370-1377 ; 30 March 2006
J Med Genet. ; 326-333 ; April 2006
Nat Genet ; 414-417 ; April 2006
Clinical Genetics ; 349-354 ; April 2006
N Engl J Med ; 1370-1377 ; 30 March 2006
J Med Genet. ; 326-333 ; April 2006
New fundamental research
New fundamental research published on PubMed
Molecular Therapy ; 556-564 ; March 2006
Nat Med ; 466-472 ; April 2006
Gene Therapy ; 587-593 ; April 2006
Nat Med ; 466-472 ; April 2006
Gene Therapy ; 587-593 ; April 2006
New clinical research
New clinical trials and research registered with Orphanet
Effect of riluzole as a symptomatic approach in patients with chronic cerebellar ataxia
High dose intravenous immunoglobulin in dermatomyositis
To register your interest in participating in a clinical trial visit Orphanet.
Clinical research results published on PubMed
MRI of the brain and cervical spinal cord in rhizomelic chondrodysplasia punctata
Axonal damage markers in cerebrospinal fluid are increased in ALS
Genotype-phenotype relationship in hereditary haemorrhagic telangiectasia
AHI1 mutations cause both retinal dystrophy and renal cystic disease in Joubert syndrome
Neurology ; 798-803 ; 28 March 2006
Neurology ; 852-856 ; 28 March 2006
J Med Genet ; 371-377 ; April 2006
J Med Genet ; 334-339 ; April 2006
Nat Med ; 401-409 ; April 2006
Neurology ; 852-856 ; 28 March 2006
J Med Genet ; 371-377 ; April 2006
J Med Genet ; 334-339 ; April 2006
Nat Med ; 401-409 ; April 2006
PartnerSearch
A resource for genetic researchers
A moderated, interactive communication and information listserver in Human Genetics available via the Internet, Hum-molgen is a resource for current human molecular genetics news and information. A free-access bulletin board through which researchers may advertise their research needs or search for offers in their area of expertise is part of Hum-molgen’s services, featuring categories such as “Biotechnical requests and sources” and “DIAGnostics - Clinical Research (professional requests)”.
Orphan Drugs
New designations & authorisations in Europe
COMP orphan drug designations in April 2006
At its meeting on 4-5 April 2006, the EMEA’s committee for Orphan Medicinal Products (COMP) adopted 9 positive opinions on orphan designation for medicinal products for the following indications:
EMEA COMP opinions in April 2006
Details of all orphan designations and authorisations granted to date by the European Commission are entered in the Community Register of Orphan Medicinal Products
Marketing authorisation granted for first biosimilar drug
Following the October 2005 regulation for similar biological medicinal products, which effectively opens the door to the EU market for “biosimilar” or “biogeneric” medicinal products, Omnitrope, produced by Sandoz, has been granted marketing authorisation by the EMEA – the first biosimilar medicine to do so. Developed for the treatment of growth disturbance and growth hormone difficiency, Omnitrope received a positive opinion from the EMEA in January (see OrphaNews Europe 17 February issue). Germany and Austria will be the first countries to receive the medicine.
New designations & authorisations in USA
FDA approves device for rare foetal disorder involving twins
The United States Food and Drug Administration (FDA), under the Humanitarian Use Device (HUD) programme, has approved a Humanitarian Device Exemption (HDE) for an instrument set designed to treat Twin-to-twin transfusion syndrome, a rare disorder of the placenta that causes blood to flow unevenly, causing one twin to receive too much blood while the other does not receive an adequate amount. The syndrome, affecting only identical twins, can cause grave complications, including severe handicaps in both twins or death during delivery. The device set contains a foetoscope and sheaths that permit intervention by laser to correct the problem. The HUD programme is specifically for medical devices for diseases affecting less than 4000 people annually in the US. To obtain HDE approval, the sponsor must be able to demonstrate the safety and probable benefit of the device.
European Rare Disease Networks Update
Eurordis studies orphan drug availability across the EU
A survey conducted by the European Organisation for Rare Diseases (Eurordis) that set out to measure the availability of orphan medicinal products across the European Union has concluded that there is a large level of disparity between Member states. Only Denmark had all twelve of the medicinal products followed in the survey available on the market for patients. The newer Member states and Luxembourg were in last place, with less than four of the medicinal products available. In addition, the study found that many products were unobtainable for patients due to the high cost of the treatment and the “non reimbursable” status accorded by certain governments. Although the legal delay to place a medicinal product on the market is 180 days, some countries are taking up to 700 days for particular products. Lengthy price negotiations with manufacturers are cited amongst the causes for delays, along with the required therapeutic value assessment for which some countries do not have adequate expertise in place to conduct. In response, Eurordis, which has been monitoring the situation for some time, proposes the creation of an EU working group composed of volunteer Member states that could assess the therapeutic added-value of a given orphan medicinal product and also negotiate an “EU ex-factory reference price” at the time the CHMP gives its opinion. The proposition has been presented to the Commission, the Committee for Orphan Medicinal Products and Industry.
Courses & Educational Initiatives
Courses
Third course in Thalassemia
The European School of Genetic Medicine presents the Third course in Thalassemia from 24-28 June 2006, in Bertinoro di Romagna, Italy. The course format will facilitate informal discussions between teachers and students.
http://www.eurogene.org:8080/body.php?t=1&l=l&p=pages/train/courses/crsprogr.php&r=78
Press & Publications
New books
The Troubled Dream of Genetic Medicine: Ethnicity and Innovation in Tay-Sachs, Cystic Fibrosis, and Sickle Cell Disease
Author: K. Wailoo and S. Pemberton
Publisher: Johns Hopkins University Press, 2006
Cutaneous T-Cell Lymphoma : Mycosis Fungoides and Sezary Syndrome
Author: H. Zackheim
Publisher: CRC, 2004
Choosing Children: The Ethical Dilemmas of Genetic Intervention
Author: J. Glover
Publisher: Oxford University Press, 2006
Press cuttings
Rare pulmonary diseases reviewed
A special issue of the journal Sarcoidosis Vasculitis and Diffuse Lung Diseases concentrates on the First International Conference on Rare Pulmonary Diseases and Orphan Drugs in Respiratory Medicine that took place in Milan, Italy in early 2005. Gathering more than 200 investigators from 9 different countries, the event served to assess "current knowledge in the fields of pathogenesis, diagnosis and therapy of rare lung disorders".
What's on where?
In May
eHealth 2006 High Level Conference and Exhibition
A review and analysis of the role eHealth plays in the progress of health policies in Europe. eHealth solutions for rare diseases will be presented and discussed.
Date: 10-12 May 2006
Venue: Malaga, Spain
Update in Neuromuscular Disorders
Examining clinical cases, assessment strategies and treatments.
Date: 17–19 May 2006
Venue: London, England
https://www.prossl.com/symposiassl/eventprog.asp?year=06&evcd=05
HUGO’s 11th Human Genome Meeting
Designed to update and increase knowledge of human genome research.
Date: 31 May–03 June 2006
Venue: Helsinki, Finland
In June
10th International Congress of Child Neurology
Presenting novel and contemporary aspects of child neurology, including a global perspective on the significant burden of neurological disease in developing countries.
Date: 11-16 June 2006
Venue: Montreal, Canada
4th International Cystinosis Conference
Families and professionals meet to discuss the challenges of everyday life for people with cystinosis as well as new scientific developments in the field.
Date: 30 June-2 July 2006
Venue: Noordwijkerhout, The Netherlands
http://www.cystinosisfoundation.org/Netherlands/PROGRAMME_AMSTERDAM_2006.pdf
In July
10th International Fragile X Conference
Hosted by the Fragile X Association of Georgia.
Date: 13-23 July 2006
Venue: Atlanta, Georgia, USA
European Working Group of Gaucher Disease
Providing an opportunity to learn about up-to-date reports on scientific discoveries and pharmaceutical initiatives and to discuss their relation to current practice.
Date: 18-22 July 2006
Venue: Cambridge, UK
In August
11th International Congress of Human Genetics
Held every five years, the 11th International Congress of Human Genetics is organised on behalf of the International Federation of Human Genetics Societies, and will be hosted by the Human Genetics Society of Australasia.
Date: 6-10 August 2006
Venue: Brisbane, Australia
2nd International Symposium on Disorders of Sex Development
"From Gene to Gender". Including a lecture on the possibilities of research efforts for rare diseases within the proposed EU framework funding programmes.
Date: 31 August-2 September 2006
Venue: Lübeck, Germany
In September
2nd Eastern European Conference on Rare Diseases and Orphan Drugs
Fostering research on rare diseases in eastern European countries.
Date: 8-9 September 2006
Venue: Plovdiv, Bulgaria
12th International Conference on Behçet’s Disease
Gathering together colleagues from specialities that range from basic research in immunology and genetics, to clinicians in rheumatology, ophthalmology, dermatology and internal medicine, and other fields.
Date: 20-23 September 2006
Venue: Lisbon, Portugal
In October
The 14th World Congress of the International Society of Psychiatric Genetics
This congress will underline the relationship between psychiatric genetics and neurosciences, with the intent of attracting participation by both clinicians and basic researchers.
Date: 28 October–1 November 2006
Venue: Cagliari, Sardinia, Italy