Population Pharmacokinetics and Exposure-Response of Luspatercept, an Erythroid Maturation Agent, in Anemic Patients With Myelodysplastic Syndromes.

ABSTRACT: Luspatercept is a recombinant fusion protein that enhances late-stage erythroid maturation. This report describes the population pharmacokinetics and exposure-response relationship of luspatercept in 260 patients with anemia due to myelodysplastic syndromes. Luspatercept displayed linear and time-invariant pharmacokinetics over a dose range of 0.125-1.75 mg/kg administered subcutaneously once every 3 weeks. Body weight was the only clinically relevant covariate of luspatercept exposure, supporting the weight-based dosing. The probability of achieving transfusion independence ≥ 8 weeks increased with time-averaged luspatercept serum exposure, reaching the plateau at doses 1.0-1.75 mg/kg. The probability of achieving multiple efficacy end points increased with slower luspatercept clearance,

SUBMITTER: Chen N 

PROVIDER: S-EPMC7376288 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature