. 2018 Nov 30;2018(1):493–506. doi: 10.1182/asheducation-2018.1.493

Table 4.

Novel agents targeting sickling

Name	Mechanism	Trial phase, type, NTC#	Primary end points	Status	Results and comments
GBT440/voxelotor	Small molecule that binds to HbS α chain and increases oxygen affinity of HbS by stabilizing it in the R-state	1/2, RDBPC, NCT02285088/ NCT03041909	Safety, PKs, PDs	Completed	All SCD genotypes; well tolerated; improvement in Hb and hemolysis⁶¹
		2a, open label, NCT02850406	PKs, change in Hb	Recruiting	Age 12-17 y; initial partial results demonstrate improved Hb and hemolysis
		3, RDBPC, NCT03036813	Hb level changes	Recruiting	All SCD genotypes; age 12-65 y
Sanguinate (PEGylated carboxyhemoglobin bovine)^*	Bovine pegylated Hb product; dual oxygen and CO transfer results in antisickling and anti- inflammatory effects	1b, open label, NCT01848925	Safety compared with HU	Completed	Well tolerated.⁶³
Sanguinate (PEGylated carboxyhemoglobin bovine)^*		2, RPC single blinded, NCT02672540/NCT02411708	Time to readiness for discharge	Completed	All SCD genotypes; interim analyses show improved RBC morphology and decreased pain scores⁶⁴
SCD 101	Unknown	1A, open label	Safety	Recruiting	Well tolerated; improved RBC morphology
SCD 101	Unknown	1B, RDBPC cross over, NCT02380079	Safety	Recruiting	Improvement in chronic pain and fatigue⁸¹

Unless otherwise specified, study included only adult patients with HbSS or HbSβ0.

PD, pharmacodynamic; RDBPC, randomized double-blind placebo control.

Study drug administered during acute VOC.