Population Pharmacokinetics and Exposure-Response of Luspatercept, an Erythroid Maturation Agent, in Anemic Patients With Myelodysplastic Syndromes.
CPT Pharmacometrics Syst Pharmacol
; 9(7): 395-404, 2020 07.
Article
in En
| MEDLINE
| ID: mdl-32602651
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, independent of effects of luspatercept exposure or disease characteristics. The probability of experiencing severe treatment-emergent adverse events decreased with increasing luspatercept exposure, especially during long-term treatment. These results provide a positive benefit-risk profile for the titration-to-response dose regimen (1.0-1.75 mg/kg) recommended for this population.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Myelodysplastic Syndromes
/
Recombinant Fusion Proteins
/
Immunoglobulin Fc Fragments
/
Activin Receptors, Type II
/
Hematinics
/
Anemia
Type of study:
Etiology_studies
Limits:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
CPT Pharmacometrics Syst Pharmacol
Year:
2020
Type:
Article
Affiliation country:
United States