PRM199 - Applications Of The Fda Guidance On Common Issues In Drug Development For Rare Diseases

Abstract

In August 2015, the US Food and Drug Administration (FDA) released a draft document to address some challenges in developing drugs for rare diseases. The following practical suggestions can be drawn from the FDA guidance. First, to adequately describe and understand the rare disease’s natural history, a disease registry should be planned strategically as part of the drug development process. One main objective of the registry would be gaining comprehensive knowledge on the disease over its clinical course and identifying the target population and important subgroups. In addition, a disease registry provides an unique opportunity to longitudinally document patient-reported outcomes such as health-related quality of life and health care utilization, which are gaining importance in post-marketing evaluations. Next, the FDA encourages the study of the disease’s pathophysiology as well as the mechanism of action of the investigative compound as fully as possible. Thorough and concrete knowledge on both will ensure effective identification of critical biomarkers that are either disease-related or associated with the compound’s pharmacologic response(s). If not already well-established, assays for those biomarkers should be developed and approved of use, ideally before the initiation of clinical trials to enhance both program efficiency and scientific validity. Drug developers should be prepared to discuss these nonclinical preparatory issues as early as possible during pre-investigational new drug application (pre-IND) meetings with the FDA. Finally, selecting appropriate efficacy endpoints for trials as the research progresses and presenting a strong case of effectiveness and safety in the end are critical to the eventual success of product approval.