Regulatory Decision Summary for Reblozyl

Authorization of Reblozyl (luspatercept for injection) was based on results from a double-blind controlled Phase III trial of adult patients with red blood cell (RBC) transfusion-dependent β-thalassemia. A total of 336 patients were randomized 2:1 to receive treatment with Reblozyl (n = 224) or placebo (n = 112).

More patients treated with Reblozyl (21%) compared to placebo (5%) achieved the primary efficacy endpoint of a ≥33% reduction in baseline RBC transfusion burden from Week 13 to 24, which is statistically significant and clinically meaningful. Greater numbers of patients treated with Reblozyl compared to patients treated with placebo (20% vs. 4%) also achieved a ≥33% reduction in baseline RBC transfusion burden from Weeks 37 to 48 (a key secondary efficacy endpoint). The efficacy of Reblozyl was also reported in more stringent secondary efficacy endpoints as more patients treated with Reblozyl compared to patients treated with placebo achieved a ≥ 50% reduction in baseline RBC transfusion burden from Weeks 13-24 (8% vs. 2%) and from Weeks 37-48 (10% vs. 1%).

Important treatment emergent adverse events (TEAEs) reported for patients treated with Reblozyl include hypertension, thrombosis, hepatic events and infections. Serious TEAEs were three times more frequent in patients treated with Reblozyl compared to patients treated with placebo including infections such as septic shock and cholangitis. Other serious TEAEs reported were anemia, cellulitis, cerebrovascular accident, deep vein thrombosis and pyrexia. Treatment discontinuation due to an adverse event occurred in more patients treated with Reblozyl compared to patients treated with placebo. The most common adverse events leading to discontinuation of Reblozyl were arthralgia, back pain, and deep vein thrombosis.

The recommended starting dose of Reblozyl is 1 mg/kg administered subcutaneously once every 3 weeks with dose titration up to 1.25 mg/kg for patients who do not achieve a reduction in RBC transfusion burden of at least one-third after two consecutive doses. Patients who do not achieve a reduction in RBC transfusion burden of at least one-third after nine weeks of treatment at the 1.25 mg/kg dose or who experience unacceptable toxicity should permanently discontinue therapy. Refer to the Product Monograph for complete Reblozyl dosing recommendations.

The safety profile for Reblozyl is acceptable for RBC transfusion dependent β-thalassemia patients who have limited treatment options when considering the reduction in RBC transfusion burden reported in the Phase III trial.

Overall, the benefit-risk profile is positive and a Notice of Compliance (NOC) was recommended for Reblozyl (luspatercept for injection), which is indicated for the treatment of adult patients with red blood cell (RBC) transfusion-dependent anemia associated with beta (β)-thalassemia. The submission was granted Priority Review.