Hundreds of Americans will converge on Capitol Hill Wednesday (March 2) to lobby for legislation that would make it easier to identify, develop and approve drugs for life-threatening rare diseases and pediatric cancers. The legislative push is part of a weeklong series of events that begins today (Feb. 29) with Rare Disease Day, established in 2008 to raise public awareness of rare diseases and their impact on patients and families.

In aggregate, 7,000 rare diseases affect an estimated 30 million Americans. Yet only 5 percent of rare diseases have a Food and Drug Administration (FDA)-approved treatment. With diagnostic tools inadequate for many of these disorders, countless numbers of rare diseases remain undiagnosed or misdiagnosed, and intervention opportunities are lost. Sadly, rare diseases disproportionately affect children, with less than a third of these children living to see their 5th birthday.

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Patient and family involvement is the single most important factor in delivering new treatments to the clinic. In my nearly two decades of experience as a physician-scientist studying Niemann-Pick type C (NPC), a rare pediatric neurodegenerative disease, I have witnessed how parents of children with this devastating disorder can have a profound impact.

After NPC afflicted three grandchildren of famed Notre Dame football coach Ara Parseghian, the family mobilized national support to create a cadre of investigators who radically altered the scientific landscape of NPC research. Over the past two decades NPC family organizations, led by the Ara Parseghian Foundation, have invested an estimated $45 million in research.

Private foundation funding filled a critical niche for researchers in identifying the genetic causes of NPC and supporting higher risk, higher impact projects that would not have been fundable via traditional founding routes, such as the National Institutes of Health (NIH). The impact of the family organizations is unmistakable. Twenty-five years ago only two labs globally were studying NPC; today there are over 50.

Through strategic partnerships, patient advocacy groups can also transform how disease-focused research is performed. Traditionally, biomedical research scientists work in their own silos at university laboratories. Innovative collaborative research models that encourage investigators to operate more like pharmaceutical industry teams, however, can be particularly effective in translating basic science advances to pre-clinical studies.

In the NPC community, several family organizations banded together to form the Support for Accelerated Research (SOAR) partnership aimed at advancing a drug to clinical testing within five years. Intent on incentivizing and modeling collaboration to accelerate the development of a treatment that would lessen the severity of their children’s devastating disease, these NPC families identified and funded scientists for whom the development of a treatment is the highest priority, sometimes even at the expense of extensive scientific knowledge.

The SOAR research collaborative functions like a virtual R&D lab, promoting an exchange of ideas and data among the scientists through biweekly calls and frequent face-to-face meetings. The collaborative speeds drug evaluation by adopting milestone-driven strategies with built-in go/no-go decision points — and reaches out to additional investigators when new expertise is needed.

Rare-disease communities also can leverage their investments by tapping into NIH resources to support early stage drug development programs. The NIH offers bench-to-bedside medical research funding designed to speed translation of promising laboratory discoveries into new medical treatments. Moreover, NIH’s recently established Therapies for Rare and Neglected Diseases (TRND) program encourages and accelerates drug development specifically for rare diseases. The program is particularly interested in developing partnerships with patient groups, and chose an NPC therapy development project as one of its first pilot projects. 

Ultimately, efficacy trials and shepherding drugs through the regulatory approval process require capital and expertise typically available only through industry partnerships. This is often straightforward for development of novel drugs for which there is intellectual property. Developing such partnerships is far more challenging if the drug has gone off patent or is being repurposed. In the latter case, U.S. orphan drug designation can help create intellectual property to stimulate investment in the rare-disease space by providing federal support to fund trials, tax credits for clinical testing costs, and exclusive rights to market the drug for seven years. Further legislation is needed to provide additional incentives to develop treatments for life-threatening rare diseases.  

NPC investigators, with NIH support, developed extensive pre-clinical data and performed early phase clinical testing of a lead drug that further served to de-risk the drug development program and incentivize industry investment. Here again, NPC patient families played a pivotal role. Some parents sought FDA permission to begin administering the drug on a “compassionate use” basis. Others successfully lobbied drug companies and investment firms to pay attention to the opportunities for developing an NPC therapy. 

Ultimately, the community’s long-term investment in science and the close partnerships forged between the patient advocacy groups and the researchers bore fruit. A pharmaceutical company, Vtesse, was founded to specifically develop this drug and is now leading the pivotal clinical trial. NPC family organizations and patient advocates play a critical role by helping Vtesse communicate effectively with the patients and families and provide transparency to the drug program.

To address the needs of a rare-disease community, diverse expertise and support are required. At the core of this effort are the patients and families themselves. On this Rare Disease Day, as we raise awareness on behalf of those affected by rare disease, we can also appreciate the vital importance of patient advocacy in achieving our goals.

Ory is professor of medicine, cell biology and physiology, Cardiovascular Division; co-director, BioMed21 Diabetic Cardiovascular Disease Center; and director of admissions, Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, Missouri.