Role of Biomarkers in Diagnosing Disease, Assessing the Severity and Progression of Disease, and Evaluating the Efficacy of Therapies

Abstract

This paper reviews biomarkers in lysosomal disease according to their categories and definitions. There are numerous biomarkers in lysosomal diseases. Some are disease or organ-specific, but most are not. Organ-specific biomarkers are especially useful, but most biomarkers help with diagnosis, assessing disease severity, prognosis, and pharmacodynamic response. There are as yet no truly validated biomarkers in lysosomal diseases by the Prentice, Fleming, and DeMets criteria. None so far can serve as surrogate endpoints in clinical trials, or as substitutes for clinically meaningful endpoints that evaluate how patients feel, function, or survive. The US Food and Drug Administration has thus far used surrogate biomarkers to license therapy only for 3 lysosomal diseases—Gaucher disease, Fabry disease, and lysosomal lipase deficiency. The paucity of surrogate biomarkers reflects success in using clinically important endpoints for the licensing of therapies for Pompe disease, mucopolysaccharidosis IVA, VI, and VII, Niemann-Pick type C, and CLN2. In conclusion, biomarkers in lysosomal diseases are best used for diagnosis, patient categorization, pharmacodynamic response, and sometimes for patient prognosis and risk. Thus far, they have been less useful as surrogate biomarkers in pivotal clinical trials.