|Other names||ACE-536, luspatercept-aamt|
|Main uses||Low red blood cells in beta thalassemia or myelodysplastic syndrome|
|Side effects||Tiredness, headache, muscle pain, dizziness, nausea, cough, allergic reactions|
|Typical dose||1 mg/kg q 21 days|
|Chemical and physical data|
|Molar mass||75958.99 g·mol−1|
Luspatercept, sold under the brand name Reblozyl, is a medication used for the treatment of low red blood cells in beta thalassemia and myelodysplastic syndrome (MDS). In MDS it is used for cases in which the risk of blood cancer is no more than moderate and erythropoietin does not work. It is given by injection under the skin.
Common side effects include tiredness, headache, muscle pain, dizziness, nausea, cough, and allergic reactions. Other side effects may include blood clots and high blood pressure. Use in pregnancy may harm the baby. It is an erythroid maturation agent which works by blocking SMAD2 and SMAD3 pathways.
Luspatercept was approved for medical use in the United States in 2019 and Europe in 2020. In the United States it costs about 11,000 USD for 75 mg as of 2021. In Canada this amount costs about 6,600 CAD. While it is approved in the United Kingdom and Europe it is not currently available there as of 2021.
Luspatercept is used in adults with transfusion dependent beta thalassemia and was shown to reduce transfusion burden by 33% compared to placebo as well as reducing serum ferritin (storage iron) concentrations. But the medication had no significant effect with regards to decreasing liver or heart iron concentrations. Possible adverse effects include temporary bone pain, joint pains (arthralgias), dizziness, elevated blood pressure (hypertension) and elevated uric acid levels (hyperuricemia). There was also an increased risk of thrombosis (blood clots) in patients who have risk factors for thrombosis who are taking luspatercept. Luspatercept is currently being evaluated for use in adults with non-transfusion dependent beta thalassemia.
It is initially given at a dose of 1 mg/kg every 21 days.
Mechanism of action
Luspatercept is a recombinant fusion protein derived from human activin receptor type IIb (ActRIIb) linked to a protein derived from immunoglobulin G. It binds TGF (transforming growth factor beta) superfamily ligands to reduce SMAD signaling. The reduction in SMAD signaling leads to enhanced erythroid maturation.
It was developed by Acceleron Pharma in collaboration with Celgene. The U.S. Food and Drug Administration (FDA) awarded orphan drug status in 2013, and fast track designation in 2015, for both indications.
The U.S. Food and Drug Administration (FDA) granted approval for luspatercept–aamt in November 2019, for the treatment of anemia (lack of red blood cells) in adult patients with beta thalassemia who require regular red blood cell (RBC) transfusions. Luspatercept was approved for medical use in the European Union in June 2020.
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