Beta-thalassemias are characterized by ineffective red blood cell ( RBC ) production, leading to anemia, iron overload, and organ failure. As current treatment options for beta-thalassemia are limited, there is a clear unmet need for alternative therapies.
Researchers have previously shown that in animal models that GDF-11, a cytokine, is produced in large quantities and participates in the decreased production of red cells.
In this study, 32 adult patients with beta-thalassemia received 0.1 ( n=8 ), 0.3 ( n=9 ), 0.5 ( n=8 ), or 0.75 ( n=7 ) mg/kg Sotatercept, a fusion protein that inhibits GDF-11, subcutaneously once every 3 weeks.
Three ( 9% ) patients reported grade greater than or equal to 2 treatment-related adverse events: 2 ( 25% ) in the 0.1 mg/kg dose cohort ( bone pain and superficial thrombophlebitis ), and 1 ( 13% ) in the 0.5 mg/kg dose cohort ( ventricular extra systoles ).
Among patients with non-transfusion-dependent beta-thalassemia ( n=22 ), a higher proportion of patients has achieved a maximum hemoglobin increase greater than or equal to 1 g/dL in the 0.3 ( 67% ), 0.5 ( 83% ), and 0.75 ( 100% ) mg/kg dose cohorts versus the 0.1 mg/kg dose cohort ( 0% ).
Furthermore, among patients with RBC transfusion-dependent beta-thalassemia ( n=10 ), a higher proportion of patients has achieved a transfusion burden reduction greater than 20% in the 0.3 ( 33% ), 0.5 ( 50% ), and 0.75 ( 67% ) mg/kg dose cohorts versus the 0.1 mg/kg dose cohort ( 0% ).
Sotatercept may be of benefit to beta-thalassemia patients with a favorable safety profile, and is also undergoing phase 2 trials for treatment of anemia in myelodysplastic syndromes, diamond blackfan anemia, chronic myelomonocytic leukemia, myelofibrosis, and end-stage renal disease. ( Xagena )
Source: European Hematology Association Congress. 2014