Some 7,000 rare diseases exist worldwide, each of which might affect as few as hundreds of individuals worldwide. While some of them are cancers, others impact the body’s metabolism, the immune system and the central nervous system – yet most of them lack an effective diagnostic tool or, very importantly, a therapy.
Such limited patient populations mean that studying these diseases and developing treatments for them is extremely complex, and conventional R&D pathways are not always adequate. So for rare diseases and the orphan drugs that treat them, collaboration of all the stakeholders is key to successful research – more than in other more prevalent diseases.
In the development of therapies for these rare diseases there are some key areas of focus: understanding the biology of the disease; enabling fast diagnosis, understanding the natural history of the disease; setting up data and knowledge-sharing systems; designing novel clinical trial designs to extrapolate safety and efficacy of medicines from a very low number of patients; and creating technologies that allow measuring outcomes in real time in patients scattered across the world.
The reality, though, is far more challenging. Patients and parents – most of these diseases affect very young children – are usually very supportive of sharing data and knowledge, of applying less conventional development pathways, and even of adopting a less conservative view on an acceptable risk level. Nevertheless we still need to make sure that evidence from safety, efficacy, quality and outcomes data from clinical trials and real-life settings is robust. Without this, registration and reimbursement – and therefore access – are a serious challenge.
The Innovative Medicines Initiative – the world’s largest public-private partnership in the life sciences sector –does not address specifically any particular rare condition. However, by harnessing the newest scientific advances to understand the biology of the diseases and progress towards more precise medicine and improved health outcomes its programmes directly support R&D into rare diseases.
Bear in mind also that, in many cases, methodologies developed in one specific area of medical science, might well be applicable across many other therapeutic areas.
IMI offers a safe harbour where companies can share data and information and combine their collective knowledge with that of academics, regulatory agencies and patients. This collaborative approach facilitates the understanding of the disease, the identification of new ways of diagnosis and the assessment of the benefit/risk profile of a candidate medicine. Programmes under IMI that cover these aspects include: E-Tox; Safe-T; EMIF; EHR4CR, and iABC.
On the novel trials design front, IMI projects embrace: pragmatic trials that address questions raised by health technology assessors and regulators alike (GETREAL); modelling and simulation (DDMORE); appropriate statistical methods aimed at cutting the numbers of patients in trials (NEWMEDS); and combinations of clinical trials and real use data (BD4BO).
Engaging patients in the R&D process to collect more reliable and relevant data and also to address the problem of smaller and scattered population marks real progress. IMI understands this and is working on: methods to assess risks and benefits (PROTECT and complementary project on patient preference elicitation that should start soon); using social media to track safety and efficacy signals (WEB-RADR); employing digital and other technologies to collect data from patients remotely (RADAR); and providing basic information online about the medicines development process to allow effective engagement in research processes (EUPATI).
IMI also aims to understand fundamental mechanisms across a range of diseases to uncover whether a single symptom is an effect of one or more causes – which may indicate a different disease in different patients. This new classification of diseases will result in more reliable clinical development and better outcomes for patients (AETIONOMY, EU-AIMS, IMIDIA, PRISM).
What we’ve outlined is just some examples of the commitment to these rare diseases, with many more projects to follow. These might address either specific rare diseases, or advanced therapies, which are often the most adequate or the only potential response to a range of rare conditions.
So IMI, while offering useful methodological insights, it also complements many other programmes at global, European and national levels, by acting as an accelerator to translate healthcare solutions from bench to bed. It’s a safe harbour that allows competing companies to get together and expose their weaknesses and strengths – something taken for granted today but unheard off 10 years ago.
If you add to this the collaboration with academia, patients, regulators, and other healthcare systems players, then you can appreciate why we believe that in IMI we’ve created a significant tool that contributes effectively to the fight against rare disease.
About the authors
Salah-Dine Chibout is the Global Head of Discovery & Investigative Safety (DIS) and Global Head Therapeutic Areas in Preclinical Safety at Novartis Institutes for BioMedical Research (NIBR). The DIS group focuses on problem solving and issue resolution related to drug safety during all phases of discovery and development of new medicines. He is responsible for a cross functional global organization operating from Cambridge, EH and Basle.
Salah-Dine has more than 22 years of experience in drug development and obtained a PhD in Molecular Immunology from the Biozentrum in Basel, Switzerland. He joined Sandoz in 1990 in the Toxicology Department. From 2008 to 2010 he was deputy Head of Translational Science in Europe.
Salah-Dine is representing Novartis at the InnoMedS Priorities Working Group in the European Federation of Pharmaceutical Industries and Associations (EFPIA). He is a Board Member of the Innovative Medicine Initiatives (IMI) which is the largest public-private partnership with the European Commission.
Carlo Incerti is Senior Vice President; Head of Global Medical Affairs at Genzyme and serves on the governing board of the Innovative Medicines Initiative.
Dr. Incerti is responsible for Global Medical Affairs, which includes Global Regulatory Affairs and Compliance, Patient Outcomes and Medical Economics/Health Outcomes, Global Patient Safety and Risk Management, Medical Operations and Medical Affairs for Rare Diseases and Multiple Sclerosis Business Units. He is a board-certified endocrinologist.4