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Accession Number
Approved, Investigational
Biologic Classification
Protein Based Therapies
Fusion proteins

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

Protein chemical formula
Not Available
Protein average weight
76000.0 Da
Not Available
  • Luspatercept
  • luspatercept-aamt
External IDs
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
LuspaterceptInjection, powder, lyophilized, for solution75 mg/1SubcutaneousCelgene2019-11-08Not applicableUs
LuspaterceptInjection, powder, lyophilized, for solution25 mg/1SubcutaneousCelgene2019-11-08Not applicableUs
Additional Data Available
  • Application Number
    Application Number

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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CAS number



Luspatercept is indicated for the treatment of anemia in adults with beta thalassemia who require regular red blood cell transfusions.6

Associated Conditions

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

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 comprised of 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

Additional Data Available
Adverse Effects

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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
Half life

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


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


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

Affected organisms
Not Available
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.
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Luspatercept.
AbituzumabThe risk or severity of adverse effects can be increased when Luspatercept is combined with Abituzumab.
AbrilumabThe risk or severity of adverse effects can be increased when Luspatercept is combined with Abrilumab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Luspatercept.
AdecatumumabThe risk or severity of adverse effects can be increased when Adecatumumab is combined with Luspatercept.
AducanumabThe risk or severity of adverse effects can be increased when Aducanumab is combined with Luspatercept.
AfelimomabThe risk or severity of adverse effects can be increased when Afelimomab is combined with Luspatercept.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Luspatercept.
AlirocumabThe risk or severity of adverse effects can be increased when Alirocumab is combined with Luspatercept.
AmatuximabThe risk or severity of adverse effects can be increased when Luspatercept is combined with Amatuximab.
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Food Interactions
Not Available


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. [PubMed:28958287]
  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. [PubMed:30617198]
  3. Camaschella C: GDF11 is not the target of luspatercept. Blood. 2019 Aug 8;134(6):500-501. doi: 10.1182/blood.2019001983. [PubMed:31395583]
  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. [PubMed:24658078]
  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. [PubMed:31394818]
  6. FDA Approved Drug Products: Reblozyl® subcutaneous injection [Link]
External Links
PubChem Substance

Clinical Trials

Clinical Trials
2Active Not RecruitingTreatmentBeta-Thalassemia1
2Active Not RecruitingTreatmentMyelodysplastic Syndromes1
2CompletedTreatmentB-Thalassemia / Beta-Thalassemia1
2Not Yet RecruitingTreatmentBeta-Thalassemia1
2RecruitingTreatmentAnemias / Primary Myelofibrosis1
2RecruitingTreatmentMyelodysplastic Syndromes1
2RecruitingTreatmentThalassaemic disorders1
3Active Not RecruitingTreatmentBeta-Thalassemia / Erythrocyte Transfusion1
3Active Not RecruitingTreatmentMyelodysplastic Syndromes1
3RecruitingTreatmentBeta-Thalassemia / Myelodysplastic Syndromes (MDS) / Myeloproliferative Neoplasm(MPN)-Associated Myelofibrosis1
3RecruitingTreatmentMyelodysplastic Syndromes1


Not Available
Not Available
Dosage forms
Injection, powder, lyophilized, for solutionSubcutaneous25 mg/1
Injection, powder, lyophilized, for solutionSubcutaneous75 mg/1
Not Available
Not Available


Experimental Properties
Not Available


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

Drug created on October 20, 2016 15:49 / Updated on December 02, 2019 09:22