A Dolon Institute report
The introduction of the EU Orphan Medicinal Products Regulation in 2000 and the Paediatric Regulation in 2006 has helped drive significant progress in the development of medicines for previously overlooked conditions. However, substantial unmet needs remain, particularly in extremely rare and paediatric-onset diseases. As policymakers consider how these frameworks should evolve, understanding what drives biopharmaceutical investment is critical to ensuring that policy changes encourage, rather than inadvertently constrain, future innovation.
Addressing unmet needs in extremely rare and paediatric-onset diseases examines these challenges through a biopharmaceutical innovation model that considers how scientific, commercial and policy factors interact to shape investment decisions. Developed by Dolon for EFPIA following a workshop with senior leaders from R&D, clinical, strategy and commercial functions, the paper applies this framework to two areas where limited treatment options remain: extremely rare diseases and paediatric-onset diseases.
The paper first explains that investment decisions evolve throughout the development journey. Early decisions are driven predominantly by scientific and clinical considerations, including understanding of the disease, viable drug targets and unmet need. Once clinical feasibility is established, commercial factors, such as the size of the patient population, potential revenue, competition and development costs, become increasingly important. These are ultimately shaped by the policy environment, including intellectual property, regulatory and pricing and reimbursement frameworks. Financial modelling brings these factors together to assess the risk-adjusted economic viability of an opportunity, with investment decisions revisited as new evidence emerges.
For extremely rare diseases, these challenges are amplified. The majority of diseases affecting fewer than one in a million people have little fundamental research, limited disease models or identified drug targets. Small patient populations also make clinical trial recruitment and adequately powered studies difficult. At the same time, the potential patient population can be more than 100,000 times smaller than in common diseases, while R&D costs per patient and development risk remain high.
The paper identifies paediatric-onset diseases as a second “white spot”, where complex disease biology, changing physiology, ethical considerations and limited validated endpoints make development particularly challenging. Regulatory requirements can add further complexity, while HTA processes may fail to recognise the broader societal value of treating children, including impacts on carers and education.
Rather than proposing a single solution, the paper argues for a portfolio of interdependent interventions. These include greater investment in basic science and patient registries, improved diagnosis and patient identification, more flexible regulatory and reimbursement approaches, proportionate CMC requirements, and meaningful incentives that improve the economic viability of development. It also explores new development models, including platform approaches and greater collaboration between industry, governments, healthcare systems, patients and non-profit organisations.
For policymakers, pharmaceutical leaders, patient organisations and other stakeholders, the paper provides a framework for understanding why unmet needs persist and where intervention could make the greatest difference.