Luspatercept (Reblozyl)

Mechanism of action

From the NCI Drug Dictionary: A soluble, recombinant fusion protein composed of a modified form of the extracellular domain of human activin receptor type IIb (ActRIIb) and linked to the human IgG1 Fc domain, with red blood cell stimulating activity. Upon subcutaneous administration, luspatercept inhibits several ligands in the transforming growth factor (TGF)-beta superfamily. This prevents activation of a variety of TGF-beta superfamily members involved in late stage erythropoiesis and results in an increased differentiation and proliferation of erythroid progenitors. Luspatercept acts at a different, later stage than erythropoietin.

Diseases for which it is used

• Beta thalassemia
• Myelodysplastic syndrome

History of changes in FDA indication

• 11/8/2019: Initial FDA approval for adult patients with beta thalassemia who require regular red blood cell (RBC) transfusions. (Based on BELIEVE)
• 4/3/2020: Approved for the treatment of anemia failing an erythropoiesis stimulating agent and requiring 2 or more red blood cell (RBC) units over 8 weeks in adult patients with very low- to intermediate-risk myelodysplastic syndromes with ring sideroblasts (MDS-RS) or with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T). (Based on MEDALIST)

History of changes in EMA indication

• 6/25/2020: Initial authorization

Also known as

• Code name: ACE-536
• Generic name: luspatercept-aamt
• Brand name: Reblozyl