Reblozyl (luspatercept-aamt) is an erythroid maturation agent.
Reblozyl is specifically indicated for the treatment of anemia in adult patients with beta thalassemia who require regular red blood cell (RBC) transfusions.
Reblozyl is supplied as an injection for subcutaneous administration. The recommended starting dose of Reblozyl is 1 mg/kg once every 3 weeks by subcutaneous injection.
If a planned administration of Reblozyl is delayed or missed, administer Reblozyl as soon as possible and continue dosing as prescribed, with at least 3 weeks between doses. Assess and review hemoglobin (Hgb) results prior to each administration. If an RBC transfusion occurred prior to dosing, the pretransfusion Hgb must be considered for dosing purposes.
If the pre-dose Hgb is greater than or equal to 11.5 g/dL and the Hgb level is not influenced by recent transfusion, delay dosing until the Hgb is less than or equal to 11 g/dL.
If a patient does not achieve a reduction in RBC transfusion burden after at least 2 consecutive doses (6 weeks) at the 1 mg/kg starting dose, increase the Reblozyl dose to 1.25 mg/kg. Do not increase the dose beyond the maximum dose of 1.25 mg/kg.
The FDA approval of Reblozyl was based on the phase 3 BELIEVE trial. The multicenter, randomized, double-blind, placebo-controlled trial enrolled 336 patients with beta thalassemia requiring regular red blood cell transfusions (6-20 RBC units per 24 weeks) with no transfusion-free period greater than 35 days during that period who were randomized 2:1 to Reblozyl (n=224) or placebo (n=112). Reblozyl was administered subcutaneously once every 3 weeks as long as a reduction in transfusion requirement was observed or until unacceptable toxicity. All patients were eligible to receive best supportive care, which included RBC transfusions; iron-chelating agents; use of antibiotic, antiviral, and antifungal therapy; and/or nutritional support, as needed. The BELIEVE trial showed a highly statistically significant improvement in the primary endpoint of erythroid response, defined as at least a 33 percent cut from baseline in red blood cell (RBC) transfusion burden with a reduction of at least two units during a defined period of 12 consecutive weeks, from weeks 13 to 24, compared to placebo. The drug also met all key secondary endpoints of statistically significant improvements in RBC transfusion burden from baseline of at least 33 percent decrease during the weeks 37 to 48 period, and at least a 50 percent reduction from week 13 to week 24, at least a 50 percent decrease from weeks 37 to 48, and a mean change in transfusion burden from weeks 13 to 24.
Adverse effects associated with the use of Reblozyl may include, but are not limited to, the following:
Reblozyl (Luspatercept-aamt) is a recombinant fusion protein that binds several endogenous TGF-β superfamily ligands, thereby diminishing Smad2/3 signaling. Luspatercept-aamt promoted erythroid maturation through differentiation of late-stage erythroid precursors (normoblasts) in mice. In a model of β-thalassemia, luspatercept-aamt decreased abnormally elevated Smad2/3 signaling and improved hematology parameters associated with ineffective erythropoiesis in mice.
For additional information regarding Reblozyl or beta thalassemia, please visit the Reblozyl web page.