Conference confirms European commitment to rare disease and orphan drug research
The European Commission conference Rare Diseases Research: Building on Success brought together members of government, science, and industry to focus on rare disease needs within the context of the opening year of the Seventh Research Framework Programme (FP7) funding scheme that runs from 2007–2013. Some central themes emerged during the course of the day: avoiding duplication of work in a field with limited resources; increasing multinational collaboration; and the need for long-term funding for many areas of rare disease research. Several speakers emphasised the relevance of rare disease research to common diseases. DG Research Deputy Director-General Zoran Stancic chaired the opening session, calling for increased sensitivity to the issue of rare diseases at the beginning of the FP7. European Commissioner for Science and Research Janez Potocnik kicked the day off with a recorded speech evoking rare diseases as a perfect example of the need for European-level research. Rare diseases, when taken together, are not so rare after all. Raising awareness and identifying the most important areas of research for the 30 million euros available for rare disease research in FP7 are important tasks to accomplish. Conference attendees were graced with the presence of H.R.H Princess Astrid of Belgium, who reminded attendees of the “distress of the entourage” surrounding the rare disease patient. She held up the Belgian neuromuscular centres of reference as a model of progress in the field. Patients are examined routinely each year in these centres.
Parliament member Alojz Peterle spoke of the need for cooperation between the European Commission and the Parliament in order to obtain results in the area of rare disease and orphan drug research.
The morning keynote speaker, French nephrologist Corinne Antignac, described the importance of studying rare diseases. She cited Bardet-Biedl syndrome, an illness that affects just 1 in 120,000 Europeans. Study of this ultra rare disease has led to the opening of new areas in cell biology. Thus, despite the rarity of the illness, some 20 international papers have been published on the disorder since 2000 in major leading medical and science journals. The completion of the human genome was elicited as an important emerging resource, along with new diagnostic tools, such as qPCR technology.
The morning topic of the one-day event was Lessons learnt from research on rare diseases. Sylvia Stockler-Ipsiroglu of University of British Columbia in Canada described the path leading to treatment via creatine replacement therapy in patients with creatine kinase deficiency. As almost always with rare disease research, the call for further progress was sounded, as the therapy developed in this case does not work in all forms of the disease, and only partially in others. Close and long-term follow-up was recommended for learning more about the natural history of the disease.
Massimo Zeviani, from Istituto Nazionale Neurologico Carlo Besta, in Milan, spoke at length of the rare disease study serving as a model for common disorders. Three examples of this were presented: retinoblastoma, which led to the discovery that cancer is a genetic disease; rare, familial Alzheimer disease, which allowed for understanding the general pathology of the disease, and the complex mitochondrial disorders, which have provided knowledge for more common disorders, such as Parkinson disease.
Gert-Jan Van Ommen from Leiden University Medical Centre spoke of rare diseases as drivers for innovation, evoking the example of Duchenne muscular dystrophy, a rare illness affecting 1 in 3500 male children, as an innovative model in which the approach of exon-skipping has proven successful. Van Ommen described the “black box” approach, in which the disease mechanism is not fully revealed until therapy or prevention is administered.
The last speaker of the morning, Carlo Incerti, representing European Biopharmaceutical Enterprises, reminded listeners of the success of the Orphan Drug regulation, in place in Europe since 2000. Although similar legislation has been in effect in the US since 1983, the EU and the US are presently producing rare disease products at a similar pace. He delineated the challenges facing rare disease therapies: few animal models; little natural history data; rare diseases that are often slowly progressing chronic diseases; extremely heterogenic phenotypes; different authorisation requirements between the US, the EU, Japan, and other countries; and limited resources to sustain long-term development with no immediate financial return. Other challenges in developing rare disease treatments include typically small patient numbers; recruitment logistics for patients often located far apart; demonstration of clinical benefits; post-authorisation commitments that can be burdensome for industry; the EU Clinical Trials Directive that adds complexity to the process; and the variance in patient access to approved medicines, depending on the country. The EMEA’s CHMP Guideline on Clinical Trials on Small Populations (February 2007) was cited as an important document for orphan drug trial design. Dr. Incerti also listed the positive aspects of orphan drug research, including the high level of innovation being applied; technologies or treatments that can provide a template for other disorders; and rare disease research and development supporting the personalised medicine concept. The necessity for a partnership between academia and industry was reiterated, with EPPOSI singled out as an example of success in this arena.
The first segment of the afternoon session was led by Leena Peltonen of the University of Helsinki and Finnish National Public Health Institute. Her discourse, Value-added by carrying out research on rare diseases at the European level investigated how population genetics can best be harnessed to aid rare disease research. She lamented the quantity of excellent science that does not translate into product. At a European level, data harmonisation is needed and available resources must be better pooled. Some European bottlenecks needing attention include a lack of expertise, an immature concept of recruitment by academia, a lack of tenure track for young experts, and underdeveloped infrastructures.
Elisabeth Tournier-Lasserve, from CNRS, INSERM and the Institut des Maladies Rares in Paris, discussed models for supporting European rare disease research. In terms of clinical characterisation, large cohorts are needed once a gene is identified for geno/pheno-typing. She cited the some 4000 rare diseases that currently have no existing molecular basis often because patients issue from one-case families. A genome platform is needed to address this. In terms of pathophysiology, for the 1800 or so rare disease genes identified to date, easy access for all European post-genomic platforms is essential. Therapeutic research currently does not have enough partnerships with industry. And as was mentioned by several speakers during the course of the day, clinical trials suffer from high costs and patient sizes that are often very small due to the rarity of an illness. The French national plan for rare diseases might well serve as a model for improving research at the EU level.
Marie Johannesson of Uppsala University Hospital and the Swedish Medical Products Agency spoke of research on rare diseases in a global context. As a member of the EMEA Paediatric Committee, she particularly evoked the need for standardised paediatric medical products that are developed with specific indications for children.
John Burn of the Institute of Human Genetics and Newcastle University in England outlined the future needs of the rare disease and orphan drug research community. As was mentioned by several speakers, long-term funding is necessary for seeing projects through to completion and to translate research into products that will truly serve the rare disease patient and family. Dr. Burn used a metaphor of the tide of medical progress carrying out the more commonplace diseases that are now cured or prevented, leaving on the sand the scattering of rare diseases that are now society’s common problem.
The day finished with a message from Christel Nourissier of EURORDIS, who brought the focus back to the patient and the force that patient groups can contribute to rare disease research and policy. DG-Research Director-General José Manual Silva Rodriguez closed the conference by reiterating the commitment of the European Commission and DG Research to the field of rare diseases and orphan medicinal products.