Drug development and regulatory considerations for ssc therapies

Drug development is an expensive and risky endeavor with an overall failure rate of ~85 % from the time drug candidates first enter the clinic to the time they reach the market. Add to this the complexity of a systemic disease with multiple proposed pathogenic mechanisms, no proven “gold standard” therapy against which to benchmark and no validated measures of disease activity, progression, or remission, and you have described a disease that one might deliberately steer away from for the purpose of developing new therapies. These diseases are often considered “intractable," and, in the absence of a major breakthrough on disease mechanism or clinical outcome assessment, they remain the territory of post-approval exploratory and investigator-initiated trials. It is in this context that this Chapter will provide a framework for understanding the preclinical, clinical, and regulatory challenges of drug development and provide insights to guide research and development strategies to advance novel drug discovery for SSc.