Regulatory Decision Summary for Reblozyl

The purpose of this Supplement to a New Drug Submission (SNDS) was to seek marketing authorization, pursuant to section C.08.004 of the Food and Drugs Regulations, for Reblozyl (luspatercept for injection) filed by Celgene Inc. for the treatment of adult patients with transfusion-dependent anemia due to very low- to intermediate-risk myelodysplastic syndromes (MDS) who have not been previously treated with an erythropoiesis stimulating agent (ESA-naïve).

Authorization of the new indication for Reblozyl (luspatercept for injection) was based on the results of an open-label, randomized, active controlled Phase 3 trial (COMMANDS) comparing the efficacy and safety of Reblozyl versus epoetin alfa in adult patients with anemia due to very low-, low-, or intermediate-risk myelodysplastic syndromes (MDS) who require red blood cell transfusions and are erythropoiesis stimulating agent (ESA)-naïve. A total of 301 patients who have completed 24 weeks of treatment or discontinued early were included in an interim efficacy analysis (i.e., 147 subjects and 154 subjects in the Reblozyl arm and epoetin alfa arm). Results showed that the study met its primary endpoint with a statistically significant and clinically meaningful improvement in red blood cell transfusion independence in patients treated with Reblozyl compared to patients treated with epoetin alfa. During treatment Week 1 to 24, 58.5% of patients in the Reblozyl arm and 31.2% of patients in the epoetin alfa arm achieved a RBC transfusion independent (RBC-TI) for 12 weeks with a concurrent mean Hgb increase ≥ 1.5 g/dL from baseline. The risk difference on the response rate was 26.6%. These results were supported with significant improvements in key secondary endpoints such as hematologic improvement-erythroid response in the Reblozyl arm compared with the epoetin alpha arm.

Overall, Reblozyl has an acceptable and manageable safety profile that is consistent with the known safety profile of Reblozyl in patients with lower risk MDS. No new safety signal was identified in the clinical trial. The most frequently reported treatment-emergent adverse events (TEAEs) in subjects treated with Reblozyl were diarrhea, fatigue, hypertension, oedema peripheral, asthenia, nausea, dyspnea, and COVID-19. A higher proportion of subjects in the Reblozyl arm compared with the epoetin alfa arm reported Grade 3 or 4 adverse events, including thrombocytopenia and hypertension. The frequency of adverse events of interest such as malignancies, premalignant disorders, kidney injury, liver toxicity, hypertension and thromboembolic events were generally consistent with the known safety profile of Reblozyl. All relevant safety findings are accurately captured in the Reblozyl Product Monograph.

The recommended starting dose of Reblozyl is 1.0 mg/kg administered subcutaneously once every 3 weeks with a step-wise dose titration to 1.33 mg/kg and then to a maximum dose of 1.75 mg/kg.

Overall, the benefit-risk profile of Reblozyl (luspatercept for injection) is positive for the treatment of adult patients with transfusion-dependent anemia due to very low- to intermediate-risk myelodysplastic syndromes (MDS) who have not been previously treated with an erythropoiesis stimulating agent (ESA-naïve).

A Notice of Compliance (NOC) was recommended.

Following review and requested revisions, the final labelling and Product Monograph were considered to be acceptable.

An updated Risk Management Plan (RMP) for Reblozyl was reviewed by Health Canada and considered acceptable.

For further details about Reblozyl, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.