Drug Development and Regulatory Considerations for Systemic Sclerosis Therapies

Drug discovery and development is an expensive and risky endeavor. It is estimated that only 10–15% of therapeutic compounds that enter clinical development ever reach the market. The challenge of developing an effective and safe drug for a rare disease such as systemic sclerosis (SSc) is arguably even greater, given the relatively rare occurrence of this complex disease, the multiple proposed pathogenic mechanisms, the heterogeneity in its phenotypic manifestation, the absence of a proven “gold standard” effective therapy against which to benchmark, the lack of validated, widely accepted instruments to measure disease activity from the clinician’s and patient’s perspective, and the scarcity of clinical research infrastructure with deep experience in the disease to efficiently conduct relatively large studies. Today, no drugs have been approved for the treatment of SSc (except for SSc-interstitial lung disease (ILD)). Moreover, the last decade was marked by multiple examples of promising candidates that failed to deliver on their promise in the clinic. However, with our ever expanding knowledge of biological disease pathways and increasing number of therapeutic modalities to target these pathways, there is a real reason for optimism and enthusiam. With the right therapeutic candidate(s), there is now, more than ever, an opportunity to bring safe and effective drugs to the market for a patient population that desperately needs it. This chapter will provide a framework for understanding the pre-clinical, clinical, and regulatory challenges of drug development and provide strategies to advance novel drug discovery and development for SSc.