Osivelotor for the treatment of sickle cell disease.

INTRODUCTION

Despite advances in the treatment of sickle cell disease (SCD), an inherited disorder leading to abnormal sickle hemoglobin (HbS) polymerization, patients continue to have a shorter life expectancy comparatively to the general population. Increase in the concentration of oxygenated HbS in red blood cells (RBCs) has been considered as a novel approach to inhibit HbS polymerization and reduce RBC sickling and their complications, raising interest for novel oxygen affinity modulators.

AREAS COVERED: This review summarizes the characteristics and primary results obtained with osivelotor, a novel oxygen affinity modulator, for the treatment of SCD. Osivelotor is presented with improved pharmacokinetic properties comparatively to voxelotor. It may enable higher hemoglobin (Hb) occupancy at lower doses potentially leading to significant improvements of clinical outcomes.

EXPERT OPINION: The first clinical phase 2/3 trial with osivelotor reported increases of Hb levels and RBC counts, and decrease of RBC sickling. The treatment was apparently well tolerated. However, osivelotor shares the same mechanism of action as voxelotor, and therefore similar limitations regarding its efficacy for which the improvement in Hb level appears misleading. Several issues remain to be resolved before considering any drug approval.