Slowly progressive, low-prevalence rare diseases with substrate deposition that result from single enzyme defects : providing evidence of effectiveness for replacement or corrective therapies Guidance for industry United States. Department of Health and Human Services United States. Food and Drug Administration Drug Development -- standards Drugs, Investigational Rare Diseases -- drug therapy Metabolism, Inborn Errors -- drug therapy This document provides guidance to sponsors on the evidence necessary to demonstrate the effectiveness of investigational new drugs or new drug uses intended for slowly progressive, low-prevalence rare diseases that are associated with substrate deposition and are caused by single enzyme defects. This guidance 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 or tissues. This guidance 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). FDA encourages sponsors to discuss with the relevant review divisions whether the approach outlined in this guidance applies to their specific drug development programs. Silver Spring, MD : Center for Drug Evaluation and Research, March 2020 United States. Department of Health and Human Services, issuing body. United States. Food and Drug Administration, issuing body. Center for Biologics Evaluation and Research (U.S.), issuing body. Center for Drug Evaluation and Research (U.S.), issuing body. Technical Report Text 1 online resource (1 PDF file (9 pages)). nlm:nlmuid-101772671-pdf 101772671 http://resource.nlm.nih.gov/101772671 English United States The National Library of Medicine believes this item to be in the public domain. https://creativecommons.org/publicdomain/mark/1.0