Population Pharmacokinetics and Exposure-Response Relationship of Luspatercept, an Erythroid Maturation Agent, in Anemic Patients With β-Thalassemia.

Journal of Clinical Pharmacology
Nianhang ChenMaria Palmisano

Abstract

β-Thalassemia is an inherited blood disorder resulting from defects in hemoglobin production, leading to premature death of red blood cells (RBCs) or their precursors. Patients with transfusion-dependent β-thalassemia often need lifelong regular RBC transfusions to maintain adequate hemoglobin levels. Frequent transfusions may lead to iron overload and organ damage. Thus, there is a large unmet need for alternative therapies. Luspatercept, a first-in-class erythroid maturation agent, is the first approved therapy in the United States for the treatment of anemia in adult patients with β-thalassemia who require regular RBC transfusions. The population pharmacokinetics and exposure-response relationship of luspatercept were evaluated in 285 patients with β-thalassemia. Luspatercept displayed linear and time-invariant pharmacokinetics when administered subcutaneously once every 3 weeks. Body weight was the only clinically relevant covariate of luspatercept clearance, favoring weight-based dosing. Magnitude and frequency of hemoglobin increase, if not influenced by RBC transfusions, was positively correlated with luspatercept area under the serum concentration-time curve (AUC), 0.2-1.25 mg/kg, whereas a significant reduction in RBC ...Continue Reading

References

Sep 16, 2005·The New England Journal of Medicine·Deborah Rund, Eliezer Rachmilewitz
Nov 15, 2007·Nature Reviews. Molecular Cell Biology·Bernhard Schmierer, Caroline S Hill
Aug 5, 2017·Lancet·Ali T TaherMaria Domenica Cappellini
Mar 27, 2020·The New England Journal of Medicine·M Domenica CappelliniUNKNOWN BELIEVE Investigators

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Citations

Feb 12, 2021·Blood Advances·Maria Domenica Cappellini, Ali T Taher
Jul 21, 2021·International Journal of Molecular Sciences·Filomena LongoAntonio Piga
Aug 19, 2021·Expert Opinion on Biological Therapy·Ali T Taher, Maria Domenica Cappellini

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NCT01749540
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NONMEM

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