Luspatercept

Luspatercept, sold under the brand name Reblozyl, is a medication used for the treatment of anemia in beta thalassemia and myelodysplastic syndromes. 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) considers it to be a first-in-class medication.
Clinical development.
Phase III trials evaluated the efficacy of luspatercept for the treatment of anemia in the hematological disorders beta thalassemia and myelodysplastic syndromes.
Structure and mechanism.
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.
History.
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.
Medical use.
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.