Emerging pharmacotherapeutic approaches for the management of sickle cell disease.

INTRODUCTION: Sickle cell disease (SCD) is an inherited disease with lifelong morbidity, whose complications include frequent acute painful vaso-occlusive episodes (VOEs) that often require hospitalization. The only pharmacotherapy currently in regular use for SCD management is hydroxyurea (hydroxycarbamide). AREAS COVERED: We review recent advances in pharmacotherapy for SCD and summarize promising synthetic agents that are in late-stage development (phase 3) for SCD. EXPERT OPINION: Emerging SCD therapies have been developed to target specific pathophysiological mechanisms of the disease, as either preventative or abortive approaches to VOEs. Continuous-use pharmacotherapeutics in late-phase development for VOE prevention include voxelotor (GBT440), which elevates hemoglobin oxygenation, and prasugrel, a platelet activation inhibitor. However, at least in the near future, it is probable that biological molecules will play a primary role in SCD preventative therapy; in combination with hydroxyurea, crizanlizumab, an anti-P-selectin monoclonal antibody, appears to reduce VOE frequency, while L-glutamine was the first substance licensed by the FDA for use in SCD in 20 years. Synthetic drugs, however, may represent key approaches for the management of individuals upon hospitalization for VOE, a major challenge for SCD. For example, rivipansel (GMI-1070), a pan-selectin inhibitor, has shown encouraging effects on hospitalization time and opioid use.