Luspatercept
Luspatercept Uses, Dosage, Side Effects, Food Interaction and all others data.
Luspatercept is a recombinant fusion protein comprised of a modified extracellular domain of activin receptor type IIB fused to the FC domain of human IgG1. It was first approved for use in the United States in November 2019 under the brand name Reblozyl® for the treatment of anemia in patients with beta thalassemia who require regular blood transfusions. Luspatercept is novel in that it ameliorates anemia via action on late-stage erythropoiesis, in contrast to typical erythropoiesis-stimulating agents (ESAs), such as darbepoetin alfa and epoetin alfa, which act only on early-stage erythropoiesis. Luspatercept's novel mechanism of action, then, is uniquely suited for the treatment of conditions in which late-stage erythropoiesis is defective, such as beta thalassemia and other myelodysplastic diseases.
Luspatercept binds to, and inhibits, several ligands that act as negative regulators of late-stage erythropoiesis, thereby alleviating the ineffective erythropoiesis observed in patients with beta thalassemia. Thromboembolic events (e.g. deep vein thrombosis, pulmonary embolism, ischemic stroke) have been reported in patients with beta thalassemia receiving luspatercept - patients with a greater baseline risk of thromboembolism may benefit from concomitant thromboprophylaxis while undergoing therapy with luspatercept. Luspatercept may carry some degree of embryo-fetal toxicity and should therefore be avoided in pregnancy. Women of child-bearing age should use an effective form of contraception during therapy and for 3 months after completion of therapy.
| Trade Name | Luspatercept |
| Availability | Prescription only |
| Generic | Luspatercept |
| Luspatercept Other Names | Luspatercept, luspatercept-aamt |
| Related Drugs | pyridoxine, Revlimid, Vitamin B6, Epogen, epoetin alfa, Retacrit, Reblozyl |
| Weight | 25mg, 75mg |
| Type | Subcutaneous powder for injection |
| Weight | 76000.0 Da |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Luspatercept is an erythroid maturation agent used to treat anemia secondary to beta thalassemia in patients requiring regular red blood cell transfusions.
Luspatercept is indicated for the treatment of anemia in adults with beta thalassemia who require regular red blood cell transfusions.
Luspatercept is also used to associated treatment for these conditions: Anemia
How Luspatercept works
Beta thalassemia is a genetic red blood cell disorder caused by mutations in the β-globin gene - these mutations cause oxidative stress and premature apoptosis of erythroblasts, thereby leading to ineffective erythropoesis. The transforming growth factor beta (TGF-β) superfamily of endogenous ligands (including activins, growth differentiation factors, and bone morphogenetic proteins) are involved in the inhibition of erythroid differentiation via activation of the Smad2/3 subfamily of intracellular effectors.
Luspatercept is a fusion protein comprising a modified extracellular domain of activin receptor type IIB (a target for many TGF-β ligands) fused to the FC domain of human IgG1. Luspatercept ameliorates ineffective erythropoiesis in patients with beta thalassemia by acting as a "ligand trap" for various members of the TGF-β superfamily, preventing their downstream signalling and subsequent inhibition of late-stage erythroid maturation. The specific members of the TGF-β superfamily targeted by luspatercept are currently unknown, though growth differentiation factor 11 (GDF11) has been experimentally excluded as a potential target.
Toxicity
Repeat-dose toxicity studies in juvenile rats showed an increase in the development of hematologic malignancies at doses of 10 mg/kg, a dose approximately 8-fold higher than the maximum recommended human dose (MRHD). Fertility studies in rats observed effects on female (but not male) fertility at doses approximately 7-fold higher than the MRHD.
Food Interaction
No interactions found.Luspatercept Hypertension interaction
[Moderate] The use of luspatercept may cause hypertension.
It is recommended to monitor blood pressure before each dose administration.
New-onset hypertension or exacerbation of preexisting hypertension should be managed with anti-hypertensive drugs as clinically appropriate.
Luspatercept Disease Interaction
Moderate: renal/liver, thromboembolism, Luspatercept – hypertension
Volume of Distribution
The average apparent volume of distribution is 7.1 L.
Elimination Route
At doses of 1 mg/kg and 1.25 mg/kg, the average steady-state AUC was 126 day•μg/mL and 157 day•μg/mL and the average Cmax was 8.17 μg/mL and 10.2 μg/mL, respectively. Steady-state was reached after 3 doses given every 3 weeks. Tmax is reached approximately 7 days after administration. Absorption pharmacokinetics do not appear to be affected by the site of subcutaneous injection.
Half Life
The average half-life of luspatercept is approximately 11 days.
Clearance
The total apparent clearance of luspatercept is 0.44 L/day.
Innovators Monograph
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