Luspatercept
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Overview
- Description
- An injectable medication that treats anemia caused by various disorders in which red blood cells are not properly produced.
- Description
- An injectable medication that treats anemia caused by various disorders in which red blood cells are not properly produced.
- DrugBank ID
- DB12281
- Type
- Biotech
- Clinical Trials
- Phase 0
- 0
- Phase 1
- 3
- Phase 2
- 21
- Phase 3
- 8
- Phase 4
- 4
Identification
- Summary
Luspatercept is an erythroid maturation agent used to treat anemia secondary to beta thalassemia, myelodysplastic syndromes, and neoplasms.
- Brand Names
- Reblozyl
- Generic Name
- Luspatercept
- DrugBank Accession Number
- DB12281
- Background
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
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Fusion proteins - Protein Chemical Formula
- Not Available
- Protein Average Weight
- 76000.0 Da
- Sequences
- Not Available
- Synonyms
- Luspatercept
- luspatercept-aamt
- External IDs
- ACE-536
Pharmacology
- Indication
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
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Anemia •••••••••••• ••••• ••••••• ••••••• ••• ••••• •••• ••••••••••••• •••••••••••••••••••••••••••••••••• •••••••• •••• •••• •••••••••••• ••• •••••••••••••• Treatment of Anemia •••••••••••• ••••• ••••••••••••••••• ••••••••••••••• ••••••••• •••• •••• ••••••••••••• ••••••• ••••••• ••• ••••• •••• •••••••••••• Treatment of Anemia •••••••••••• ••••• •••••••• •••• ••••••••••••••• ••••••••• •••• •••• ••••••••••••• ••••••• ••••••• ••• ••••• •••• •••••••••••• Treatment of Anemia •••••••••••• ••••• •••••••••••••• ••••••••••• •••••••••••• •••••••• •••• ••••••••••••••• ••••••••• ••••••• ••••••• ••• ••••• •••• •••••••••••• Treatment of Anemia •••••••••••• ••••• •••••••••••••• ••••••••••• •••••••••••• ••••••••••••••••• ••••••••••••••• •••••••••• ••••••• ••••••• ••• ••••• •••• •••••••••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
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
- Absorption
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
- Metabolism
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
- Clearance
The total apparent clearance of luspatercept is 0.44 L/day.6
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
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
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- 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.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Reblozyl Injection, powder, for solution 75 mg Subcutaneous Bristol Myers Squibb Pharma Eeig 2020-12-16 Not applicable EU Reblozyl Powder, for solution 25 mg / vial Subcutaneous Bristol Myers Squibb 2020-11-23 Not applicable Canada Reblozyl Injection, powder, for solution 25 mg Subcutaneous Bristol Myers Squibb Pharma Eeig 2020-12-16 Not applicable EU Reblozyl Injection, powder, lyophilized, for solution 75 mg/1 Subcutaneous Celgene Corporation 2019-11-08 Not applicable US Reblozyl Powder, for solution 75 mg / vial Subcutaneous Bristol Myers Squibb 2020-11-23 Not applicable Canada
Categories
- ATC Codes
- B03XA06 — Luspatercept
- Drug Categories
- Activin Receptors
- Amino Acids, Peptides, and Proteins
- Antianemia Drugs
- Antianemic Preparations
- Blood and Blood Forming Organs
- Enzymes
- Enzymes and Coenzymes
- Erythroid Maturation Agents
- Globulins
- Hematinics
- Hematologic Agents
- Immunoglobulin Constant Regions
- Immunoglobulin Fragments
- Immunoproteins
- Intracellular Signaling Peptides and Proteins
- Membrane Proteins
- Peptide Fragments
- Peptides
- Phosphotransferases
- Phosphotransferases (Alcohol Group Acceptor)
- Protein Kinases
- Protein-Serine-Threonine Kinases
- Proteins
- Receptors, Growth Factor
- Receptors, Peptide
- Receptors, Transforming Growth Factor beta
- Recombinant Proteins
- Transferases
- Chemical TaxonomyProvided by Classyfire
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- AQK7UBA1LS
- CAS number
- 1373715-00-4
References
- General References
- 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]
- 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]
- Camaschella C: GDF11 is not the target of luspatercept. Blood. 2019 Aug 8;134(6):500-501. doi: 10.1182/blood.2019001983. [Article]
- 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]
- 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]
- FDA Approved Drug Products: Reblozyl (luspatercept-aamt) for subcutaneous injection [Link]
- FDA Approved Drug Products: REBLOZYL (luspatercept-aamt) for injection, for subcutaneous use (August 2023) [Link]
- External Links
- PubChem Substance
- 347911311
- 2262544
- Wikipedia
- Luspatercept
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Completed Not Available Myeloid Dysplasia 1 somestatus stop reason just information to hide Not Available Completed Treatment Adult Granulosa Cell Tumor of the Ovary 1 somestatus stop reason just information to hide Not Available Recruiting Not Available Acute Myeloid Leukemia / Myelodysplastic Syndrome / Primary Myelofibrosis (PMF) 1 somestatus stop reason just information to hide Not Available Recruiting Not Available Autoimmune Hemolytic Anemia / Autoimmune Neutropenia / Chronic Idiopathic Neutropenia / Cold Agglutinin Disease (CAD) / Immune Thrombocytopenia (ITP) / Myelodysplastic Syndrome 1 somestatus stop reason just information to hide Not Available Recruiting Not Available Beta-Thalassemia Major 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, powder, for solution Subcutaneous 25 MG Injection, powder, for solution Subcutaneous 75 MG Injection, powder, lyophilized, for solution Subcutaneous 25 mg/1 Injection, powder, lyophilized, for solution Subcutaneous 75 mg/1 Powder, for solution Subcutaneous 25 mg / vial Powder, for solution Subcutaneous 75 mg / vial Solution Subcutaneous 37.500 mg Powder 25 mg Powder 75 mg Injection, powder, for solution Subcutaneous 50 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
Drug created at October 20, 2016 21:49 / Updated at September 02, 2023 00:24