Guide on Rare Diseases with Substrate Deposition

FDA has published a final guidance on “Slowly Progressive, Low-Prevalence Rare Diseases With Substrate Deposition That Result From Single Enzyme Defects: Providing Evidence of Effectiveness for Replacement or Corrective Therapies.” The document discusses the evidence necessary to demonstrate the effectiveness of investigational new drugs or new drug uses intended for such therapies. It applies only to those low-prevalence rare diseases with well-characterized pathophysiology, and in which changes in substrate deposition can be readily measured in relevant tissue, the agency says. It does not apply to products intended for low-prevalence rare diseases with rapidly progressive clinical courses — “such conditions can be evaluated by traditional approaches (i.e., using clinical endpoints such as survival, preservation of function, etc.) — or low-prevalence rare diseases with previously characterized endpoints predictive of clinical benefit (e.g., normalization of phenylalanine levels for phenylketonuria patients),” it adds. FDA says sponsors should discuss with the relevant review divisions whether the approach outlined in the guidance applies to their drug development programs.