Emerging drugs for the treatment of sickle cell disease: a review of phase II/III trials.

Abstract

Introduction: The substitution of glutamic acid by valine on the ß-globin chain produces the hemoglobin S variant responsible for sickle cell disease (SCD), a disorder that affects millions of people worldwide and leads to acute and cumulative organ damage. Even though life expectancy has significantly improved where the best medical care is available, there are still few therapeutic options for SCD and those are limited by their availability, cost, and individual toxicities.

Areas covered: This review summarizes the clinical data on current treatments for SCD and emerging therapies studied in the acute setting as well as potential disease-modifying agents, with an emphasis on the FDA-approved agents.

Expert opinion: Hydroxyurea has been a gold standard for two decades, showing benefits in acute complications and overall survival in sickle cell anemia, although data is lacking for certain genotypes such as hemoglobin SC. As progress is made in our understanding of the pathophysiological networks characterizing SCD, numerous pathways appear to be targetable, with L-glutamine, crizanlizumab and voxelotor now approved by the FDA. Pursuing a multi-agent approach could alter the disease course in a more effective fashion and provide an alternative option to curative therapies, but longer clinical studies are needed.