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 transfusion-dependent anemia resulting from very low- to intermediate-risk myelodysplastic syndromes (MDS) who have ring sideroblasts and who have failed or are not suitable for erythropoietin-based therapy. A total of 229 patients were randomized 2:1 to receive Reblozyl (n = 153) or placebo (n = 76). The primary endpoint on study was the proportion of MDS patients who did not require red blood cell (RBC) transfusions over any consecutive fifty-six day (8-week) period from Week 1 through Week 24. A key secondary endpoint was the proportion of patients who did not require RBC transfusions over any consecutive eighty-four day (12-week) period from Week 1 through Week 24.

The study met its primary and key secondary endpoint with statistically significantly higher rates of RBC-transfusion independence observed in patients treated with Reblozyl compared to patients treated with placebo. Thirty-eight percent of patients treated with Reblozyl compared to thirteen percent of patients treated with placebo did not require a RBC transfusion for any 8-week period during Week 1 to Week 24. For the more stringent secondary outcome of RBC transfusion independence for at least 12 weeks from Week 1 to Week 24, twenty-eight percent of patients treated with Reblozyl achieved this outcome compared to only eight percent of patients treated with placebo.

The most frequently reported treatment-emergent adverse events (TEAEs) were fatigue, diarrhea, asthenia, nausea, dizziness dyspnea, and back pain, which were each reported at ≥5% higher incidence with Reblozyl compared to placebo. Less common but serious TEAEs reported in MDS patients treated with Reblozyl included basal cell carcinoma, angina, atrioventricula block, kidney failure and pneumonia.

The recommended starting dose of Reblozyl is 1 mg/kg administered subcutaneously once every 3 weeks with dose titration to 1.33 mg/kg and then to a maximum dose of 1.75 mg/kg for patients who still require RBC transfusions after two consecutive doses at the current dosing level. Patients should discontinue Reblozyl if they do not achieve a response after 9 weeks of treatment at the maximum dose or if unacceptable toxicity occurs at any time.

Overall, the benefit-risk profile is positive and a Notice of Compliance (NOC) was recommended for Reblozyl (luspatercept for injection) for the treatment of adult patients with transfusion-dependent anemia requiring at least two RBC units over 8 weeks resulting from very low- to intermediate-risk myelodysplastic syndromes (MDS) who have ring sideroblasts and who have failed or are not suitable for erythropoietin-based therapy.