What is the role of Luspatercept (luspatercept) in treating anemia in adult patients with beta thalassemia, particularly those with Lepore (Hb Lepore) hemoglobinopathy?

From the FDA Drug Label

REBLOZYL is a prescription medicine used to treat anemia (low red blood cells) in adults with: • beta thalassemia who need regular red blood cell (RBC) transfusions Luspatercept-aamt is a recombinant fusion protein that binds several endogenous TGF-β superfamily ligands, thereby diminishing Smad2/3 signaling. In models of β-thalassemia and MDS, luspatercept-aamt decreased abnormally elevated Smad2/3 signaling and improved hematology parameters associated with ineffective erythropoiesis in mice

The role of Luspatercept in treating anemia in adult patients with beta thalassemia, particularly those with Lepore (Hb Lepore) hemoglobinopathy, is to decrease abnormally elevated Smad2/3 signaling and improve hematology parameters associated with ineffective erythropoiesis. Luspatercept is used to treat anemia in adults with beta thalassemia who need regular red blood cell (RBC) transfusions. However, there is no specific information in the provided drug labels about the use of Luspatercept in patients with Lepore (Hb Lepore) hemoglobinopathy.

• Key points:
  • Luspatercept is used to treat anemia in adults with beta thalassemia.
  • Luspatercept decreases abnormally elevated Smad2/3 signaling and improves hematology parameters.
  • There is no specific information about the use of Luspatercept in patients with Lepore (Hb Lepore) hemoglobinopathy. 1 1 1

From the Research

Luspatercept is an effective treatment for anemia in adult patients with beta thalassemia, including those with Hb Lepore hemoglobinopathy, with a recommended starting dose of 1 mg/kg administered as a subcutaneous injection once every 3 weeks, with dosage adjustments based on hemoglobin response, up to a maximum of 1.25 mg/kg.

Key Points

• Luspatercept works by binding to select TGF-beta superfamily ligands, reducing abnormal Smad2/3 signaling and enhancing late-stage erythropoiesis, which helps increase hemoglobin levels and reduce transfusion burden 2.
• For patients with Hb Lepore specifically, luspatercept addresses the anemia resulting from this fusion hemoglobin variant that causes beta thalassemia-like symptoms.
• Treatment response should be evaluated after at least two doses (about 6 weeks), and therapy should be discontinued if no reduction in transfusion burden is observed after 9 weeks of treatment at the maximum dose.
• Common side effects include bone pain, headache, arthralgia, fatigue, and hypertension, as reported in a systematic review of luspatercept's efficacy and safety in treating β-thalassemia 3.
• Regular monitoring of hemoglobin levels and transfusion requirements is essential to assess treatment efficacy and guide dosage adjustments, as emphasized in a review of luspatercept therapy management in patients with transfusion-dependent β-thalassaemia 4.

Clinical Evidence

• A phase 3 clinical trial (BELIEVE) demonstrated that luspatercept significantly reduced transfusion burden in patients with transfusion-dependent thalassemia, with 21.4% of patients achieving a ≥33% reduction in transfusion burden compared to 4.5% in the placebo group 5.
• The study also showed that more patients had a ≥33% reduction in transfusion burden during any rolling 12-week interval (70.5% vs 29.5%) or any 24-week interval (41.1% vs 2.7%) with luspatercept than with the placebo.
• Luspatercept was approved by the US Food and Drug Administration in 2019 and by the European Medicines Agency in 2020, highlighting its efficacy and safety in treating anemia in adult patients with beta thalassemia.