The trials and hopes for drug development in sickle cell disease.

Although sickle cell disease (SCD) is highly prevalent worldwide, it is a rare disease in the United States and Europe. Over the past decade, there has been an increased understanding of the pathophysiology of SCD. While multiple drugs have been tested, only one drug, hydroxycarbamide, is approved by the relevant regulatory agencies specifically for this disease. Due to the combination of an improved understanding of disease pathophysiology, governmental support and the success of several recently approved drugs for other orphan diseases, there is an increased interest in the development of targeted drugs for SCD. Novel drugs that are currently being evaluated include haemoglobin F inducers, anti-sickling agents, anti-oxidants, anti-adhesive agents, anti-inflammatory agents, anticoagulants and anti-platelet agents. In addition to the evaluation of acute pain crisis as a study endpoint, clinical trials employing other SCD-related complications, exercise capacity, as well as patient reported outcomes are warranted and necessary in order to advance the development of these novel therapeutic agents. Finally, despite the availability of multiple biomarkers, many of these are of limited clinical value in SCD and require further assessment in prospective studies to validate their prognostic importance before they are acceptable as surrogate endpoints.