Table 4. [Sickle Cell Disease: Targeted Therapies]. - GeneReviews®

Treatment Class	Specific Therapy	Mechanism of Action	Dose	Comments
Disease-modulating pharmacotherapy	Hydroxyurea	Induction of HbF synthesis Metabolized into nitric oxide, a potent vasodilator	20 mg/kg, titrated to maximum tolerated dose	Results in ↓ sickling & ↑ RBC survival ↓ WBC, reticulocyte, & platelet counts ↓ cell adhesion & overall improvement in blood flow ↓ vascular inflammation
L-glutamine	Antioxidant	Oral (Note: Dose is weight-dependent; see medication package insert.)
Voxelotor	Binds hemoglobin & ↑ its affinity for oxygen	Oral (Note: Dose is weight-dependent; see medication package insert.)
Crizanlizumab	Antibody to P-selectin; ↓ cell adherence to endothelium, which ↑ microvascular blood flow	5 mg/kg IV infusion once per month
Transplantation	HSCT	Replace SCD-producing marrow w/compatible marrow from a donor w/o SCD or a donor with sickle cell trait
Gene therapy	Exagamglogene autotemcel (exa-cel) (autologous ex vivo CRISPR/Cas9 gene editing)	Activation of HbF by inhibiting Bcl11a activity in erythroid cells ¹
Lovotibeglogene autotemcel (lovo-cel) (autologous ex vivo lentiviral vector gene therapy)	Production of anti-sickling hemoglobin (HbA^T87Q) ²

Treatment Class

Specific Therapy

Mechanism of Action

Dose

Comments

Disease-modulating pharmacotherapy

Hydroxyurea

Induction of HbF synthesis
Metabolized into nitric oxide, a potent vasodilator

20 mg/kg, titrated to maximum tolerated dose

Results in ↓ sickling & ↑ RBC survival
↓ WBC, reticulocyte, & platelet counts
↓ cell adhesion & overall improvement in blood flow
↓ vascular inflammation

L-glutamine

Antioxidant

Oral (Note: Dose is weight-dependent; see medication package insert.)

Voxelotor

Binds hemoglobin & ↑ its affinity for oxygen

Oral (Note: Dose is weight-dependent; see medication package insert.)

Crizanlizumab

Antibody to P-selectin; ↓ cell adherence to endothelium, which ↑ microvascular blood flow

5 mg/kg IV infusion once per month

Transplantation

HSCT

Replace SCD-producing marrow w/compatible marrow from a donor w/o SCD or a donor with sickle cell trait

Gene therapy

Exagamglogene autotemcel (exa-cel) (autologous ex vivo CRISPR/Cas9 gene editing)

Activation of HbF by inhibiting Bcl11a activity in erythroid cells ¹

Lovotibeglogene autotemcel (lovo-cel) (autologous ex vivo lentiviral vector gene therapy)

Production of anti-sickling hemoglobin (HbA^T87Q) ²

From: Sickle Cell Disease

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Adam MP, Feldman J, Mirzaa GM, et al., editors.

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