New white paper outlines three paradigm shifts to overcome barriers to orphan drug development

A new cross-industry white paper argues that improving patient identification, advancing understanding of rare disease biology, and adopting broader approaches to value assessment could help overcome longstanding barriers to orphan drug development.

The Baseline            

• A new cross-industry white paper identifies patient identification, disease biology, and value assessment as key barriers limiting orphan drug development.
• The report highlights the potential of AI and real-world data (RWD) to improve rare disease diagnosis, evidence generation, and clinical development.
• The authors call for broader collaboration and more comprehensive value frameworks to support innovation and investment in rare disease therapies.

Despite regulatory incentives in Europe and the US, approximately 95% of the more than 10,000 identified rare diseases still have no approved treatment, affecting an estimated 400 million people worldwide. Against this backdrop, the new white paper ‘Drive For Change: Paradigm Shifts and Strategic Recommendations to Overcome Barriers in Orphan Drug Development’ sets out a series of strategic recommendations aimed at improving research, investment, and evidence generation for rare diseases.

Developed by leaders from Volv Global, Sanofi, Fondation Ipsen, Unitechpharma, and patient advocacy organization brave2change, the paper draws on workshops and surveys conducted at the World Orphan Drug Congress 2023, involving industry professionals and patient representatives from 25 countries.

The authors argue that progress is being constrained by three fundamental challenges:

1. Inaccurate estimates of patient populations
2. Incomplete understanding of rare disease biology
3. Narrow approaches to assessing the economic and societal burden of disease

According to the paper, addressing these issues together could improve both clinical development and the commercial viability of orphan drug programs.

A key focus of the paper is the potential role of AI and real-world patient data in identifying undiagnosed patients and generating more accurate prevalence estimates. Case studies presented in the paper indicate that Volv Global's inTrigue methodology identified a patient population for a neuroendocrine tumor indication approximately 3.2-times larger than a sponsor's previous epidemiological estimate. The paper also reports that a UK primary care pilot for Fabry and Pompe disease was associated with a 50% to 100% increase in diagnosis rates after a decade in which diagnosis rates had remained unchanged.

The paper also recommends greater use of natural history studies and RWD to improve understanding of disease progression, patient heterogeneity, and clinically meaningful endpoints. It also argues that health technology assessment and value assessment frameworks should better capture the broader economic and societal burden of rare diseases, including delayed diagnosis, productivity losses, and caregiver burden.

Reflecting on the paper's recommendations, Léon van Wouwe, Clinical Innovation Director at Volv Global and lead author, said:

“Throughout my career in clinical development, I have seen the same barriers slow the progress of novel treatments – and time and again, the root cause is the same: as an industry, we do not adequately understand the lived clinical experience of patients, both before and after diagnosis. Today, we have more tools to do exactly that than ever before. Drive For Change is a call to use them.”

The authors conclude that greater collaboration between pharmaceutical companies, healthcare providers, regulators, payers and patient organizations, alongside wider use of RWD and AI-enabled analytical approaches, could help strengthen orphan drug development, support evidence generation, and accelerate innovation for rare diseases.