The safety and efficacy of the agents and/or uses under investigation have not been established. There is no guarantee that the agents will receive health authority approval or become commercially available in any country for the uses being investigated.
Proposed Mechanism of Action
Luspatercept-aamt (ACE-536) is a recombinant fusion protein with a modified extracellular domain of the human activin receptor type IIB (ActRIIB) linked to a human immunoglobulin G1 (IgG1) Fc domain.1,2 Luspatercept-aamt was shown in preclinical studies to bind several endogenous transforming growth factor (TGF)-β superfamily ligands that regulate late-stage erythropoiesis.1-3 The TGF-β superfamily regulates Smad2/3 signaling, which preclinical studies have suggested contributes to ineffective erythropoiesis.1-3 In preclinical studies, luspatercept-aamt has been shown to function as a ligand trap for TGF-β ligands, thereby diminishing abnormally elevated Smad2/3 signaling.2,3 This is hypothesized to underlie the effects of luspatercept-aamt on promoting erythroid maturation through differentiation of late-stage erythroid precursors.2
Luspatercept Proposed Mechanism of Action