Ultragenyx – The promise of new technologies to treat rare diseases will be realized only if we revolutionize our regulatory approach


Article Byline: Lisa M. Kahlman, executive director public policy & public affairs, Ultragenyx

Developing therapies for rare and ultrarare diseases is challenging for myriad reasons: patient populations are small;the progression of these diseases is often slow and varies from person to person;clinical symptoms are often irreversible;and the existing regulatory framework, which mainly relies on trials that assess clinical outcomes over a period of many years, is not designed to appropriately assess rare diseases and their potential treatments.

We currently have new technology — such as gene and cell therapies, mRNA and antisense oligonucleotides — that can treat more diseases than ever. We also have a ready-made regulatory framework: the accelerated approval pathway, which involves relying on surrogate endpoints and biomarkers in lieu of clinical endpoints to shorten the time to approval. This is critical in cases where it is impractical to collect sufficient clinical outcomes data within a reasonable time frame, and will be the only way that some of these new technologies can be approved to treat rare diseases. Yet, the accelerated approval pathway is still primarily used in the oncology space and its benefits are not being applied to many rare genetic diseases. There is a misconception that relying on biomarkers and surrogate endpoints could lead to the approval of expensive therapies that may not actually improve patient outcomes. But, there are specific types of biomarkers — primary disease biomarkers — that directly and precisely represent the underlying disease and can rapidly and effectively accelerate the cycle time for drug discovery, clinical study and approval, resulting in dramatically improved therapies that treat the underlying disease optimally.

It has been difficult to gain acceptance of these types of biomarkers from the U.S. Food and Drug Administration (FDA), even when a clear scientific basis exists. Ultragenyx has been pushing for the FDA to use the accelerated approval pathway in cases where the science for using biomarkers is clear and may be the only route to developing new drugs.

In February of this year, we supported a workshop with the Reagan-Udall Foundation for the FDA entitled, “Qualifying Biomarkers to Support Rare Disease Regulatory Pathways.” We are hopeful that public forums like this will pave the way to clear and consistent regulatory guidance that supports the use of accelerated approval for rare and ultrarare diseases.