Workshop 14: 2024 Scientific Workshop

2024 Scientific Workshop Summary

Watch the 2024 Recording

Workshop Goals

1. Identify the considerations and implications of establishing a statutory definition for ultra rare diseases and the metrics that would generate an evidence-based definition should one be recommended.  
2. Examine the current state of therapy development for very small population diseases to document who is benefitting from systems in place, who is being left behind and where there are opportunities for targeted policy change.  

Background  

Rare diseases impact over 30 million Americans across more than 10,000 diseases. The Orphan Drug Act established that a rare disease was defined as one affecting less than 200,000 people and it created a series of incentives for therapy developers to meet the treatment needs of these smaller communities through tax credits, fee waivers, and a potential 7- years of market exclusivity after approval. Despite the increased momentum in rare disease therapy development following the ODA, only 5% of the known rare diseases currently have FDA approved therapies.   

Unfortunately, conditions with very small populations, often referred to as ultra-rare conditions, face increased difficulties with novel therapy development. Not only do these disease groups face difficulty in hosting clinical trials due to low prevalence, but there are unique regulatory, funding, and research hurdles as a result, begging the question: 

How do we establish a framework to ensure success in therapy development for conditions with very small patient populations?   

Generating momentum for new resources or regulatory changes for small, rare disease populations may require tying such requests to a formal characterization or definition of “ultra rare”, guiding who becomes eligible for new programs or flexibilities. Recent experience suggests that policy changes without such a definition are unlikely to move forward, but given the significant potential for unintended consequences, it is imperative that any such definition in statute be well thought out and grounded in evidence justifying why a different framework or set of resources is needed.    

This conversation is emerging globally as different countries and regulatory bodies establish informal and formal definitions of ultra rare for approval and health technology assessment purposes. The European Medicines Agency (EMA) and several other health authorities informally consider a disease to be ultra rare if it effects less than 1 in 50,000 while many in the U.S. have established their own suggested thresholds between 2,000 and 20,000.  The common threads in these definitions are the lack of a scientifically backed justification for the chosen cutoff and trepidation to establish such a formal cutoff for fear of the potential repercussions.  

Recognizing the complexities involved with defining whether an ultra-rare distinction was necessary and what the implications and opportunities of such an approach might be, the EveryLife Foundation advocated for funding to allow the National Academy of Sciences to produce a report that would convene expert stakeholders to establish what data is needed to define ultra-rare, which critical stakeholders are required for this determination, where the data gaps for determining this definition are, and to identify opportunities to define ultra-rare outside of population. This appropriations work builds on previous efforts to expand ultra-rare therapeutics opportunities through the ALTITUDE Program in the STAT Act that aimed to reform trial design and regulatory issues, as well as the guide detailing successful approaches to clinical trials for small, heterogenous patient populations that resulted from the EveryLife Foundation 2019 Scientific Workshop.  

It stands to reason with the global uncertainty of defining ultra-rare and best practices for supporting the community in the orphan drug space, we host a conversation to engage the rare disease community to undertake an evidence-based approach to documenting and defining the legislative and regulatory policy needs that will advance therapy development for the ultra-rare population.   

Questions?  

Contact Baillie McGowan, Associate Director of Policy and Research 

bmcgowan@rareadvocates.org