The recommended starting dose of Reblozyl is 1 mg/kg given as a subcutaneous injection once every 3 weeks. Reblozyl should be administered by a healthcare professional. Hemoglobin (Hgb) should be assessed and reviewed prior to each administration. If an RBC transfusion occurred prior to dosing, dosing considerations should be based on the pretransfusion Hgb. Hgb. If the pre-dose Hgb is ≥ 11.5 g/dL and the Hgb is not influenced by recent transfusion, Reblozyl should be delayed until the Hgb is ≤ 11 g/dL.

If a reduction in RBC transfusion burden is not achieved after at least 2 consecutive doses (6 weeks) at the 1 mg/kg starting dose, the Reblozyl dose should be increased to, but not exceeding, the maximum dose of 1.25 mg/kg. If a patient experiences a response followed by a lack of or lost response to Reblozyl, the patient should be assessed for causative factors (e.g., a bleeding event). Reblozyl should be discontinued if a patient does not experience a decrease in transfusion burden after 9 weeks of treatment (administration of 3 doses) at the maximum dose, or if unacceptable toxicity occurs at any time.

Luspatercept-aamt is an erythroid maturation agent. Luspatercept-aamt is a receptor fusion protein consisting of a modified extracellular domain of the human activin receptor type IIB linked to a human IgG1 Fc domain with a calculated molecular mass of approximately 76 kD. Luspatercept is produced in Chinese hamster ovary cells by recombinant DNA technology.

The efficacy of Luspatercept-aamt was evaluated in adult patients with beta thalassemia in the BELIEVE trial (NCT02604433). BELIEVE was a multicenter, randomized, double-blind, placebo-controlled trial in which (n=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 were randomized 2:1 to Luspatercept-aamt (n=224) or placebo (n=112). In BELIEVE, Luspatercept-aamt 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 excluded patients with a diagnosis of Hemoglobin S/β-thalassemia (sickle cell) or isolated alpha (α)-thalassemia (e.g., Hemoglobin H) or who had major organ damage (liver disease, heart disease, lung disease, renal insufficiency). Patients with recent deep vein thrombosis or stroke or recent use of ESA, immunosuppressant, or hydroxyurea therapy were also excluded.

The efficacy of Luspatercept-aamt in adult patients with beta thalassemia was established based upon the proportion of patients achieving RBC transfusion burden reduction (≥33% reduction from baseline) with a reduction of at least 2 units from Week 13 to Week 24. 21.4% of patients achieved > 33% reduction in RBC transfusion burden vs. 4.5% of patients treated with placebo.