"Alone we are rare, together we are strong." - NORD motto

There are approximately 7,000 rare diseases that in aggregate affect 5% of the worldwide population. Rare diseases seem a lot less rare, though, when we recognize that approximately 300 million people globally are living with a rare disease, a number nearly equivalent to the population of the United States.

The impact of rare disease on children is especially devastating. Seventy percent of genetic rare diseases start in childhood, and all pediatric cancers are rare.

With few treatment options (less than 10% of rare diseases have FDA-approved treatments) and a small, dispersed community who can share knowledge and experiences, the rare disease experience is notoriously isolating. Fortunately, that is changing. 

While the differences in rare diseases can be vast, the many foundations and increasing number of companies that work within this space are finding that their rarity binds them. Their commonalities have led to the development of coalitions like the Rare Cancer Coalition within the National Organization for Rare Disorders, the Rare Disease Company Coalition, and the Coalition Against Childhood Cancer. These organizations are unified around identifying the systemic barriers that can hinder rare disease progress and innovating to break down the barriers.

What is becoming more obvious is that the rare disease space is offering models of cross-stakeholder collaboration and advocacy for legislation that recognizes and adjusts the medical research system to incentivize rare disease research. The good news is that this is building a better research system for all of us.

Philanthropy has been a major driver of change in the rare disease space, stepping in to fill major voids in support of progress, especially as it pertains to seed funding of promising and innovative projects and de-risking therapeutic research and discovery, in addition to advocacy. These efforts have led to major therapeutic successes in rare disease areas, and regulatory incentives that have paved the way for industry and biotech companies to enter the rare disease space. To highlight a few:

  • Cystic Fibrosis (CF) is a rare genetic disorder that results in thick and sticky mucus that can cause severe damage to the lungs, digestive system, and other organs that secrete mucus. The Cystic Fibrosis Foundation has supported the team of scientists that discovered the CF gene, the companies that developed therapies that address the devastating symptoms of CF, and ultimately implemented a venture philanthropy model to drive $40 million of funding to Aurora Biosciences (now Vertex Pharmaceuticals). All of this led to the development of Kalydeco, the first drug to address the underlying cause of CF.
  • Amyotrophic Lateral Sclerosis (ALS) is a rare neurodegenerative disease during which nerve cells in the brain and spinal cord break down, reducing muscle functionality. When Amylyx Pharmaceutical's AMX0035 gained approval as a treatment for ALS, it was not without significant support – both financial and relational -- from philanthropy. Target ALS provided Amylyx co-founders with connections to experts in the field. Pre-clinical efforts were the result of collaboration with the Project ALS Therapeutics Core at Columbia while a phase two clinical trial was made possible with funding from the ALS Association and ALS Finding a Cure, and clinical trial infrastructure was supported by Sean M. Healey and the AMG Group.
  • Neuroblastoma is a rare type of cancer most often diagnosed in children younger than five that forms from immature nerve cells in the adrenal glands, abdomen, chest, and the nerve tissue near the spine. Unituxin is the first approved drug specifically developed for treatment of children with high-risk neuroblastoma. The St. Baldrick's Foundation supported the investigator who spearheaded the development of this immunotherapy and supported the clinical trials that led to Unituxin FDA approval. Solving Kids' Cancer worked alongside a range of other charities to push for the expansion of the use of this immunotherapy to England and Wales. Moreover, the St. Baldrick's advocacy program played a key role in development and promotion of the Creating Hope Act, which provides market incentives to pharmaceutical companies to develop drugs for rare pediatric diseases.

There are lessons from these accomplishments that donors can use to replicate success in other disease areas. Among the most significant are:

  1. Support collaborative sample and data networks, not only financially, but with the contribution of patient samples and data. With limited patient numbers, every piece of data from every patient sample collected at diagnosis and along the treatment journey is essential to understanding the disease etiology and path. It is only with aggregate and longitudinal data that we will fully understand the biology of diseases and develop effective therapies. Data and sample repositories that provide resources from international sites openly to the research community are critical, and many of these repositories, especially for rare diseases, receive philanthropic support.
  2. Commit to strategic and sustained funding of research that de-risks potential therapeutics for smaller patient populations. Funding for high-risk research within the translational funding gap is less likely to be supported with federal or industry funds.
  3. Advocate for legislation that will incentivize improved rare disease research infrastructure. For example, revamped clinical trial infrastructure has the potential to shift clinical trials toward agile protocols that: (1) assign patients to clinical trials based on therapies that are most appropriate for the disease subtype, (2) shift patients quickly off of clinical trials that are not benefiting them and onto alternative protocols, (3) loop clinical trial data back into enrollment requirements to enable adaptation of trials as they are occurring, and (4) improve equity by providing decentralized structures or opening clinical trials at more sites. These innovations are coming, but regulatory flexibility will continue to pave the way for improvements.

Even those diseases that were once considered common are being broken out into subtypes that benefit from unique treatment options. For example, the childhood brain cancer medulloblastoma is now divided into at least four distinct molecular subgroups, each with discrete molecular, clinical, and prognostic characteristics with the potential to direct therapy selection that can lead to improvement in patient outcomes.

Outcomes for more common and extrinsic diseases have improved significantly. We are now entering a phase of medical research where we can no longer rely on the infrastructure that has been successful in bringing treatments for common diseases into the marketplace.

Innovations that are essential in the rare disease space will need to become commonplace for research to continue to drive impact. The good news is that rare disease innovations have the potential to change systems and drive progress across all disease spaces, not only rare ones. 

Everyone – researchers, regulators, clinicians, pharmaceutical and biotech companies, philanthropists, and advocates – can embrace the lessons learned from the rare disease space to accelerate progress, and recognize the outsized role that philanthropy will play in driving progress by supporting innovation in the rare disease space.