FDA awards six grants for natural history studies in rare diseases

The U.S. Food and Drug Administration (FDA) announced it has awarded six new research grants for natural history studies in rare diseases. The aim of the research is to inform medical product development by better understanding how specific rare diseases progress over time.

One potential application of these studies is the opportunity to eventually use natural history models to augment the need for placebo arms in studies of drugs that target very rare disease, where trial recruitment can be challenging.

This is the first time the FDA is providing funding through its Orphan Products Grants Program to conduct rare disease natural history studies. The FDA is providing a total of $6.3 million over the next five years to fund four natural history studies. In addition, through a partnership with the National Institutes of Health’s (NIH) National Center for Advancing Translational Sciences (NCATS), the FDA received $3.5 million to be combined with FDA funding to fund an additional two studies. NCATS’ support was made possible through its Therapeutics for Rare and Neglected Diseases (TRND) program.

“We believe these important studies will provide key information about how these rare diseases develop and progress and can ultimately help in the development of models of disease behavior that can make the development process more efficient,” said FDA Commissioner Scott Gottlieb, M.D. “We’ve been working overtime to develop models that can simulate the behavior of placebo arms in the setting of very rare diseases, where recruiting for clinical trials can be especially hard. We’re grateful to NCATS for its support of this important program, which enabled us to extend our support to two additional studies.”

The natural history of a disease is the course a disease takes from its onset, through the presymptomatic and clinical stages, to a final outcome in the absence of treatment. Because the natural history of many rare diseases remains relatively unknown, efficiently developing diagnostics and therapeutics for these patients poses big challenges.

“One of the challenges we encounter developing therapies for rare diseases is the lack of natural history data to guide the design of successful clinical trials,” said Nora Yang, Ph.D., director of portfolio management and strategic operations in NCATS’ Division of Pre-Clinical Innovation. “We are pleased that we can collaborate with the FDA to fund two natural history studies this year that will help NCATS develop novel treatments for patients who suffer from these devastating diseases.”

The FDA received more than 80 grant applications that were reviewed and evaluated for scientific and technical merit by more than 60 rare disease and natural history experts, which included representatives from academia, patient groups, NIH and the FDA. The six studies awarded cover a broad spectrum of diseases and address unmet needs.

Grants being funded by the FDA:

• Children's Hospital of Philadelphia, David Lynch, Prospective study in Friedreich’s ataxia, approximately $2 million over 5 years


• Columbia University Medical Center, Adi Cohen, Prospective study in pregnancy and lactation-associated osteoporosis, approximately $2 million over 5 years


• University of Iowa, Alicia Gerke, Retrospective study in sarcoidosis, approximately $300,000 over 2 years


• University of North Carolina at Chapel Hill, Kenneth Ataga, Prospective study in sickle cell anemia to determine biomarkers of endothelial function changes in chronic kidney disease, approximately $2 million over 5 years

The two additional grants primarily being funded by NIH/NCATS include:

• Children’s Hospital Corporation, Wen-Hann Tan, Prospective study in Angelman syndrome, approximately $2 million over 5 years


• University of Utah, Nicholas Johnson, Prospective study in Myotonic Dystrophy Type 1 to Determine Biomarkers and Clinical Endpoints, approximately $2 million over 5 years

Congress appropriates funding to the FDA for the study of rare diseases. The FDA is using these funds for the Orphan Products Grants Program to support natural history studies as well as clinical trials.

Rare diseases, as defined by the Orphan Drug Act, are diseases or conditions with a prevalence of less than 200,000 persons in the United States. Though the diseases are individually rare, together, the 7,000 known rare diseases affect approximately 30 million Americans.