Reblozyl is a recombinant fusion protein that binds to multiple endogenous TGF-β superfamily ligands, thereby reducing Smad2/3 signaling. Reblozyl promotes erythrocyte maturation by differentiating late erythroid precursors (normal blasts) in mice. In models of β-thalassemia and MDS, Reblozyl reduced abnormally elevated Smad2/3 signaling and improved hematological parameters associated with ineffective erythropoiesis in mice.
Clinical trial efficacy of Reblozyl
Clinical trials: β-thalassemia trials
The BELIEVE trial (NCT02604433) evaluated the efficacy of Reblozyl in adult patients with β-thalassemia. This was a multicenter, randomized, double-blind, placebo-controlled trial of 336 subjects who were receiving regular RBC transfusions (6-20 RBC units every 24 weeks). All patients were randomized 2:1 to receive Reblozyl plus best supportive care (n=224) or placebo plus best supportive care (n=112) after a transfusion-free period of more than 35 days.
The median age of all subjects was 30 years (range: 18-66 years), 42% were male, and consisted of 54.2% white, 34.8% Asian, and 0.3% black or African American.
The evaluation of Reblozyl efficacy was based on the proportion of patients who achieved a reduction in RBC transfusion burden (reduction of more than 33% from baseline), with a reduction of at least 2 units from week 13 to week 24.
The results are as follows: At 13-24 weeks of treatment, 21.4% of patients in the rotercept group had a red blood cell transfusion burden reduced by more than 33% compared with the start of the study, which was significantly better than the placebo group (4.5%). At 37-48 weeks of treatment, 10.3% of patients in the rotercept group had a red blood cell transfusion burden reduced by more than 50% compared with the start of the study, while the placebo control group was 0.9%.
The efficacy of rotercept was evaluated in the MEDALIST trial (NCT02631070), which is a multicenter, randomized, double-blind, placebo-controlled trial in patients with intermediate-risk myelodysplastic syndrome with very low IPSS-R, low or requiring red blood cell transfusion (2 or more red blood cell units within 8 weeks).
A total of 229 trial participants were randomly divided into the rotercept treatment group (n=153) and the placebo control group (n=76) in a 2:1 ratio. Randomization was stratified according to baseline red blood cell transfusion burden and baseline IPSS-R. 1 mg/kg subcutaneously every 3 weeks; the dose can be increased after completing the first 2 cycles if the patient has received at least one RBC transfusion in the first 6 weeks. Two dose level increases were allowed (to 1.33 mg/kg and 1.75 mg/kg).
The median age of the 229 study participants was 71 years (range: 26-95 years). 63% of the trial population was male and 69% was white.
The efficacy of Reblozyl was evaluated based on the proportion of patients who achieved RBC independence (RBCTI), defined as no RBC transfusion for 8 consecutive weeks during weeks 1-24.
The results are as follows: The proportion of patients who achieved RBC independence in the Reblozyl treatment group was significantly higher than that in the control group. The proportion of patients who achieved RBC independence for more than 12 weeks in the Reblozyl group was 33.3% during weeks 1-48, which was significantly higher than that in the control group (11.8%).
