NATIONAL HARBOR, Maryland — Clinical development in the world of rare diseases is “on the verge of tremendous progress, with increased understanding of inherited and acquired genetic diseases,” Janet Woodcock, MD, acting commissioner of the US Food and Drug Administration (FDA) said at the 2021 World Orphan Drug Congress, as she answered questions posed by Edward Neilan, MD, chief medical and scientific officer of the National Organization for Rare Disorders (NORD).

Dire need during the coronavirus disease 2019 (COVID-19) pandemic has contributed to the record acceleration of vaccines, and this expedited timeline has potential benefits for the rare disease community. Dr. Woodcock analyzed the factors that allowed for such speed in vaccine development, including prioritization and large amounts of funding funneled into the development of these products.

She also remarked that telemedicine has allowed “remote visits to work well” within a clinical trial setting, while simultaneously “decreasing the burden to those with rare diseases who must travel long distances to participate in such trials.” Remote informed consent has also transformed the way clinical trials are run.

Regarding the varying approaches to clinical trials, Dr. Woodcock described “Master Protocols,” which can be supported with the advent of telemedicine and remote access to trials to study and collect data on rare diseases. She encouraged patients suffering from a specific disease to band together to collect data and provide a comprehensive natural history background so researchers may better understand disease mechanisms and symptoms. This way, they may decide upon clinical trial endpoints that are meaningful to patients’ experience and will improve disease outcomes incrementally.

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One challenge in determining a specific meaningful endpoint in rare disease is that several patients with the same disease may experience diverse symptoms, Dr. Woodcock said. The symptoms that most bother one person may not be as relevant to another individual with the same disease.

Recognition of the individual differences in response to intervention and the uniqueness of each person with a rare disease due to various factors will guide the development of precision medicine for future generations, she explained. A possible solution to this problem would be to establish multiple predefined endpoints and stack multiple areas of concern into a single endpoint weighted by the severity of the symptom.

The patient plays a major role in the drug development process, Dr. Woodcock said, noting that patient organizations inform drug development by providing natural history data, especially those involving disease progression. Difficulties conducting research within rare disease arise due to small patient populations and lack of disease information, so patient experience and input are critical in providing the foundation for such research. Once researchers comprehend the disease process and what is most important to the patient, the risk of failing to complete or delaying a study due to lack of practicality may be reduced.

Dr. Neilan referenced the Bespoke Gene Therapy Consortium, a collaboration between the FDA Center for Biologics and Research, NORD, and the National Center for Advancing Translational Science (NCATS). He emphasized the need to create “economies of scale” with regard to regulatory innovation in the field of rare diseases. Given that there are more than 7000 rare diseases, Dr. Woodcock affirmed the economical practicality of establishing a “reusable vector where researchers can plug in the varying symptoms and sequences for each rare disease” to spare time and cost.

With the Prescription Drug User Fee Act (PDUFA) set to be reauthorized by the FDA in September 2021, Dr. Woodcock confirmed the FDA will support additional funding and allocation of resources in the fields of cell and gene therapies and other treatment innovations for rare diseases. The FDA will also continue to support the review and regulation of regenerative medicine in the future, she said.


New world of clinical development for rare diseases. Presented at: World Orphan Drug Congress USA 2021: August 26, 2021; National Harbor, MD.