Stakeholders Provide Insight to CDER on Educational Needed in Rare Disease Development

The United States Food and Drug Administration (FDA) Center for Drug Evaluation and Research (CDER) recently sought comments on its Learning and Education to Advance and Empower Rare Disease Drug Developers (LEADER 3D) initiative in its Accelerating Rare disease Cures (ARC) program. In response, two dozen stakeholders submitted comments on what topics they believe are important knowledge gaps to cover in such educational materials.

Input and Research

One of the suggestions centered around the importance of patient input when it comes to rare diseases. This is because expert opinions may not fund a complete understanding of the unmet need for a rare disease patient population. According to the Dravet Syndrome Foundation, “Early-engagement of therapeutic developers with patient populations and patient advocacy groups will facilitate a development process focused on improvements that are truly impactful to rare disease patients.”

Similarly, the American Society of Clinical Pharmacology and Therapeutics proposed the use of more case studies to educate sponsors on successful (and failed) cases of rare disease drug development. The comment notes that “it is important for these sessions to not only bring the successful case studies that emphasize the FDA’s flexibility, but also identify the enablers for such flexibility by showing failure cases.”

The National Organization for Rare Disorders (NORD) submitted comments emphasizing the importance of not only educating medical professionals, but also patients. NORD noted that not only does the educational material for lay persons need to be published, but it needs to be available in a space where it can be easily found and shared, as “the best educational materials are useless if the intended audience cannot find them.”

Trial Considerations

The Pharmaceutical Research and Manufacturers of America (PhRMA) and Biotechnology Innovation Organization (BIO) submitted a joint comment regarding the lack of guidance on dose finding and exposure-response for rare disease studies. “We note that while recent guidance has referenced dose finding and exposure-response studies in rare disease contexts, the guidance does not expand on regulatory flexibilities for clinical pharmacology studies in rare disease populations.” The organizations went on to recommend the FDA “develop educational materials that specifically address the challenges of assessing dose response and exposure in small patient populations.”

Praxis Precision Medicines also submitted a comment, noting that there are inconsistencies with how the term “rare disease” is defined, even within the agency. “Ensuring a flexible, yet consistent interpretation of the definition for rare diseases will ensure that patients with life-threatening and severely debilitating disease…are able to more quickly access treatments that could be life-altering.”

The Rare Disease Company Coalition cited the role real-world evidence can play in rare diseases, saying “natural history data and real-world evidence can help to define rare disease progression, novel biomarkers, genetic relationships, and treatment effects.” The comment went on to note that the FDA’s current guidance does provide a framework for the collection of real-world evidence but there are gaps in addressing the standardization of the data. Therefore, the Coalition asks the FDA to provide additional guidance to sponsors about real-world evidence “that is fit-for purpose and constitutes regulatory-grade data.”

What’s Next?

Additional comments can be found on the docket here.

CDER extended the timeline for comments in response to a request from PhRMA and BIO and comments on the proposal were due April 30, 2023.