The Journey of Commitment to Ultra-Rare Disease Patients: A Supportive Business Model


Over the last 5 years, more than 4000 FDA-regulated clinical trials were initiated worldwide for rare disease treatments.

Biopharmaceutical companies have made tremendous progress in advancing innovations for the treatment of rare diseases, with more than 600 products approved to date. Rare diseases now account for 31% of the overall research and development pipeline, which is up from 18% in 2010, according to the Tufts Center for the Study of Drug Development Impact Report.

Over the last 5 years, more than 4000 FDA-regulated clinical trials were initiated worldwide for rare disease treatments, which represents a significant increase in the number of studies focused on this much needed area of development.

However, even with these advances, 95% of rare diseases have no treatment options. This gap underscores the difficult journey many patients experience and must compel the biopharmaceutical industry to commit meaningful action to advance scientific discovery and development for these diseases.

There is still tremendous work to be done and we must continue to close the gap in the number of treatments and the sheer number of rare diseases. The effect of these diseases on patients and families is devastating, but the socioeconomic impact is also crushing. Improving the number of treatments for these patients would not only make an enormous impact on individual lives, but also on society.

To contribute towards eliminating this disparity, rare disease patient communities have become adept at developing natural history data for a target indication. Natural history studies are important for understanding rare diseases—the cause(s), range of manifestations, and progression—as well as for raising awareness.

Importantly, well-conducted natural history studies can also yield information on biomarkers, as well as other markers of clinical outcomes, which can be immensely important in the successful design of clinical trials. They can even serve as comparator arms for studies in which it may be impractical to randomize patients to placebo.

Many communities have successfully created robust natural history registries that have not only resulted in an increased understanding of the disease, but also in the study of new and meaningful treatments. Advocacy organizations dedicated to supporting patients, families, and research for conditions such as cystic fibrosis and spinal muscular atrophy (SMA), represented by the Cystic Fibrosis Foundation and Cure SMA, respectively, both started robust patient registries to collect valuable natural history data.

This information has been instrumental in the development of life-saving new treatments over the past several years for these 2 devastating diseases. Driven by necessity, patients and their families are often the ones who are working to bring forward therapies for their children or themselves.

Additionally, the discovery of new genomic technologies and medicines now allows for the rapid understanding and development of treatment options even for very small cohorts of patients, such as patients with ultra-rare diseases. The parents of a young girl named Lydia have done just that. Early in her young life, Lydia started experiencing seizures and subquently missed many of her developmental milestones—a parent’s worst nightmare.

She was diagnosed with an epileptic encephalopathy caused by a single genetic mutation—a spontaneous typo—in a critical gene called KCNQ2. There are no specific treatments for KCNQ2-mediated epileptic encephalopathies, so Lydia’s parents, Rohan and Jen Seth, took matters into their own hands.

They believe that Lydia and children like her with spontaneous mutations can be helped if we target the source with individualized treatments. Discovering that much of the current pharmaceutical model was not set up to address these rare mutations, they started the Lydian Accelerator to help fund their daughter's N-of-1 antisense oligonucleotides (ASOs) treatment and open source that knowledge.

ASOs are a string of nucleotides that can be designed to silence a mutation such as Lydia’s. Their mission is to create a freely available set of processes to enable more developers of other ASOs for N-of-1 disease scenarios. With each treatment, their hope is that other patients and familiars re-use or advance components of the treatment and reduce the time and cost to develop personalized therapies for these rare genetic mutations.

The Yellow Brick Road Project is another wonderful example of a patient organization that has emerged from the needs of patients and families. In 2016, a neurodevelopmental disorder caused by spontaneous mutations in the HNRNPH2 gene on the X-chromosome was discovered in patients.

Via full exome sequencing, just 6 girls were initially identified. Their parents have embarked on a journey together to build an organization that funds multiple programs to help study the natural history of the disease, elucidate the function of the gene, develop an animal model, and drive patient identification.

A world class scientific board has been formed and new insights have been gained on the mechanism disease as well as potential therapeutic approaches using splicing technologies or gene therapy approaches. In a collaboration between the foundation and leading genomic companies, the application of artificial intelligence, facial recognition, and social media initatives, more than 80 patients have been identified and the next wave of outreach and technology will drive those numbers higher.

You can see that patients and families have done an incredible job advocating for a greater understanding of their disease and finding creative solutions to advancing potential therapeutics, however, we can do better for all patients. As an industry, it is our obligation to better support these patients and families because no one should be left behind based on the rarity of their disease.

The biotech and pharmaceutical industries have the resources, expertise and infrastructure in place to make a more meaningful impact for rare disease communities. We should support basic research, the establishment of patient advocacy groups, the development of registries or natural history studies, and the organization of international forums to help these patients.

In response to this urgent need, patient communities, government agencies, and the biopharmaceutical industry are coming together to develop innovative models to address the significant needs of these rare communities. There is an increasing sector within biotech that believes that as an industry, we have an ethical responsibility to create innovative business models to support patients with rare and ultra-rare diseases with no available treatments.

We are starting to see some exciting companies formed specifically to support these patients. If the fundamental understanding of the biological pathway and the treatment modality exists, and the biopharmaceutical community has the ability to execute on development, we have an obligation to make sure that no patient is left behind.

In addition, I challenge each company in our industry to step up and consider funding at least one pro-bono program in which the economic returns are limited to the cost of development, but where the return on investment for patients, families, and our society will have an incredible social and economic benefit.

It is a privilege to help these patients. Together as an industry, we can continue to think innovatively to help these under-served patient populations. If each biotech or pharma company took on one disease, with a commitment to helping patients for the cost of development, think about the incredible benefit we could bring to all members of the human race.

Chris Adams, PhD, MBA, is founder and chief executive officer of Cydan.


U.S. Food and Drug Administration (FDA) Office of Orphan Products Development (OOPD):

America’s Biopharmaceutical Companies:

Tufts Impact Report:

H2 referrence:

Yellow Brick road:

Lydian accelerator

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