Luspatercept is an erythroid maturation agent used to treat anemia secondary to beta thalassemia, myelodysplastic syndromes, and neoplasms.

Brand Names
Generic Name
DrugBank Accession Number

Luspatercept is a recombinant fusion protein comprised of a modified extracellular domain of activin receptor type IIB fused to the FC domain of human IgG1.2,6 It was first approved for use in the United States in November 2019 under the brand name Reblozyl® for the treatment of anemia in patients with beta thalassemia who require regular blood transfusions.6 Luspatercept is novel in that it ameliorates anemia via action on late-stage erythropoiesis, in contrast to typical erythropoiesis-stimulating agents (ESAs), such as darbepoetin alfa and epoetin alfa, which act only on early-stage erythropoiesis.4 Luspatercept's novel mechanism of action, then, is uniquely suited for the treatment of conditions in which late-stage erythropoiesis is defective, such as beta thalassemia and other myelodysplastic diseases.4,5

Approved, Investigational
Biologic Classification
Protein Based Therapies
Fusion proteins
Protein Chemical Formula
Not Available
Protein Average Weight
76000.0 Da
Not Available
  • Luspatercept
  • luspatercept-aamt
External IDs
  • ACE-536



Luspatercept is indicated for the treatment of:

  • Anemia in adults with beta thalassemia who require regular red blood cell transfusions.6
  • Anemia without previous erythropoiesis stimulating agent use (ESA-naïve) in adult patients with very low- to intermediate-risk myelodysplastic syndromes (MDS) who may require regular red blood cell (RBC) transfusions.7
  • Anemia failing an erythropoiesis stimulating agent and requiring two or more RBC units over eight 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).7
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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofAnemia•••••••••••••••••••••••• ••••••• ••• ••••• •••• ••••••••••••• •••••••••••••••••••••••••••••••••• •••••••• •••• •••• •••••••••••• ••• ••••••••••••••
Treatment ofAnemia•••••••••••••••••••••••••••••••••• ••••••••••••••• ••••••••• •••• •••• ••••••••••••• ••••••• ••••••• ••• ••••• •••• ••••••••••••
Treatment ofAnemia••••••••••••••••••••••••• •••• ••••••••••••••• ••••••••• •••• •••• ••••••••••••• ••••••• ••••••• ••• ••••• •••• ••••••••••••
Treatment ofAnemia••••••••••••••••••••••••••••••• ••••••••••• •••••••••••• •••••••• •••• ••••••••••••••• ••••••••• ••••••• ••••••• ••• ••••• •••• ••••••••••••
Treatment ofAnemia••••••••••••••••••••••••••••••• ••••••••••• •••••••••••• ••••••••••••••••• ••••••••••••••• •••••••••• ••••••• ••••••• ••• ••••• •••• ••••••••••••
Contraindications & Blackbox Warnings
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Luspatercept binds to, and inhibits, several ligands that act as negative regulators of late-stage erythropoiesis, thereby alleviating the ineffective erythropoiesis observed in patients with beta thalassemia.6,2 Thromboembolic events (e.g. deep vein thrombosis, pulmonary embolism, ischemic stroke) have been reported in patients with beta thalassemia receiving luspatercept - patients with a greater baseline risk of thromboembolism may benefit from concomitant thromboprophylaxis while undergoing therapy with luspatercept.6 Luspatercept may carry some degree of embryo-fetal toxicity and should therefore be avoided in pregnancy. Women of child-bearing age should use an effective form of contraception during therapy and for 3 months after completion of therapy.6 Luspatercept may also lead to the development of extramedullary hematopoietic (EMH) masses in adult patients with transfusion-dependent beta-thalassemia.6

Mechanism of action

Beta thalassemia is a genetic red blood cell disorder caused by mutations in the β-globin gene - these mutations cause oxidative stress and premature apoptosis of erythroblasts, thereby leading to ineffective erythropoesis.2 The transforming growth factor beta (TGF-β) superfamily of endogenous ligands (including activins, growth differentiation factors, and bone morphogenetic proteins) are involved in the inhibition of erythroid differentiation via activation of the Smad2/3 subfamily of intracellular effectors.2,1,4

Luspatercept is a fusion protein comprising a modified extracellular domain of activin receptor type IIB (a target for many TGF-β ligands) fused to the FC domain of human IgG1.1,2,3 Luspatercept ameliorates ineffective erythropoiesis in patients with beta thalassemia by acting as a "ligand trap" for various members of the TGF-β superfamily, preventing their downstream signalling and subsequent inhibition of late-stage erythroid maturation. The specific members of the TGF-β superfamily targeted by luspatercept are currently unknown, though growth differentiation factor 11 (GDF11) has been experimentally excluded as a potential target.3


At doses of 1 mg/kg and 1.25 mg/kg, the average steady-state AUC was 126 day•μg/mL and 157 day•μg/mL and the average Cmax was 8.17 μg/mL and 10.2 μg/mL, respectively.6 Steady-state was reached after 3 doses given every 3 weeks. Tmax is reached approximately 7 days after administration.6 Absorption pharmacokinetics do not appear to be affected by the site of subcutaneous injection.

Volume of distribution

The average apparent volume of distribution is 7.1 L.6

Protein binding

Not Available


As luspatercept is a fusion protein, it is expected to undergo catabolism into amino acids by general protein degradation processes.6

Route of elimination

Not Available


The average half-life of luspatercept is approximately 11 days.6


The total apparent clearance of luspatercept is 0.44 L/day.6

Adverse Effects
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Repeat-dose toxicity studies in juvenile rats showed an increase in the development of hematologic malignancies at doses of 10 mg/kg, a dose approximately 8-fold higher than the maximum recommended human dose (MRHD).6 Fertility studies in rats observed effects on female (but not male) fertility at doses approximately 7-fold higher than the MRHD.6

Not Available
Pharmacogenomic Effects/ADRs
Not Available


Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
No interactions found.


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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ReblozylInjection, powder, lyophilized, for solution25 mg/1SubcutaneousCelgene Corporation2019-11-08Not applicableUS flag
ReblozylInjection, powder, for solution75 mgSubcutaneousBristol Myers Squibb Pharma Eeig2020-12-16Not applicableEU flag
ReblozylPowder, for solution25 mg / vialSubcutaneousCelgene2020-11-23Not applicableCanada flag
ReblozylInjection, powder, for solution25 mgSubcutaneousBristol Myers Squibb Pharma Eeig2020-12-16Not applicableEU flag
ReblozylInjection, powder, lyophilized, for solution75 mg/1SubcutaneousCelgene Corporation2019-11-08Not applicableUS flag


ATC Codes
B03XA06 — Luspatercept
Drug Categories
Chemical TaxonomyProvided by Classyfire
Not Available
Organic Compounds
Super Class
Organic Acids
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Alternative Parents
Not Available
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available
Affected organisms
Not Available

Chemical Identifiers

CAS number


General References
  1. Mies A, Platzbecker U: Increasing the effectiveness of hematopoiesis in myelodysplastic syndromes: erythropoiesis-stimulating agents and transforming growth factor-beta superfamily inhibitors. Semin Hematol. 2017 Jul;54(3):141-146. doi: 10.1053/j.seminhematol.2017.06.004. Epub 2017 Jul 4. [Article]
  2. Piga A, Perrotta S, Gamberini MR, Voskaridou E, Melpignano A, Filosa A, Caruso V, Pietrangelo A, Longo F, Tartaglione I, Borgna-Pignatti C, Zhang X, Laadem A, Sherman ML, Attie KM: Luspatercept improves hemoglobin levels and blood transfusion requirements in a study of patients with beta-thalassemia. Blood. 2019 Mar 21;133(12):1279-1289. doi: 10.1182/blood-2018-10-879247. Epub 2019 Jan 7. [Article]
  3. Camaschella C: GDF11 is not the target of luspatercept. Blood. 2019 Aug 8;134(6):500-501. doi: 10.1182/blood.2019001983. [Article]
  4. Suragani RN, Cadena SM, Cawley SM, Sako D, Mitchell D, Li R, Davies MV, Alexander MJ, Devine M, Loveday KS, Underwood KW, Grinberg AV, Quisel JD, Chopra R, Pearsall RS, Seehra J, Kumar R: Transforming growth factor-beta superfamily ligand trap ACE-536 corrects anemia by promoting late-stage erythropoiesis. Nat Med. 2014 Apr;20(4):408-14. doi: 10.1038/nm.3512. Epub 2014 Mar 23. [Article]
  5. Kubasch AS, Platzbecker U: Setting Fire to ESA and EMA Resistance: New Targeted Treatment Options in Lower Risk Myelodysplastic Syndromes. Int J Mol Sci. 2019 Aug 7;20(16). pii: ijms20163853. doi: 10.3390/ijms20163853. [Article]
  6. FDA Approved Drug Products: Reblozyl (luspatercept-aamt) for subcutaneous injection [Link]
  7. FDA Approved Drug Products: REBLOZYL (luspatercept-aamt) for injection, for subcutaneous use (August 2023) [Link]
PubChem Substance

Clinical Trials

Clinical Trials
4Not Yet RecruitingTreatmentMyelodysplastic Syndrome1
4RecruitingTreatmentThalassemia Major / Transfusion-dependent Anemia1
3Active Not RecruitingTreatmentMyelodysplastic Syndrome1
3CompletedTreatmentBeta-Thalassemia / Erythrocyte Transfusion1


Not Available
Not Available
Dosage Forms
Injection, powder, for solutionSubcutaneous25 MG
Injection, powder, for solutionSubcutaneous75 MG
Injection, powder, lyophilized, for solutionSubcutaneous25 mg/1
Injection, powder, lyophilized, for solutionSubcutaneous75 mg/1
Powder, for solutionSubcutaneous25 mg / vial
Powder, for solutionSubcutaneous75 mg / vial
SolutionSubcutaneous37.500 mg
Injection, powder, for solutionSubcutaneous50 mg
Not Available
Not Available


Experimental Properties
Not Available

Drug created at October 20, 2016 21:49 / Updated at September 02, 2023 00:24