Regulatory Decision Summary for Sarclisa

The marketing authorization for Sarclisa (isatuximab for injection) was based on results of a multicentre, randomized, open-label, active controlled phase III study in patients with relapsed and refractory multiple myeloma who had received at least two prior therapies including lenalidomide and dexamethasone. Treatment with Sarclisa in combination with pomalidomide and dexamethasone (Isa-Pd) demonstrated a 40% reduction in the risk of disease progression or death compared with the control pomalidomide and dexamethasone therapy. The objective response rate (ORR) was also 25% (1.7-fold) higher in the Isa-Pd group versus the Pd group. The reduction in disease progression or death as well as the improvement in ORR were statistically significant and considered clinically meaningful.

The addition of Sarclisa to pomalidomide and dexamethasone was associated with increases in severe or serious adverse events. The most common adverse reactions in the Isa-Pd group were infections, neutropenia and infusion-related reactions. There was also an increased risk of diarrhea, nausea, and vomiting. Cardiac arrhythmias and second primary malignancies occurred more commonly in patients treated with Isa-Pd; the role of Sarclisa in these events cannot be ruled out. Adverse reactions of Sarclisa in combination with pomalidomide and dexamethasone were generally manageable by dosage adjustment and symptomatic treatments (e.g., granulocyte colony stimulating factor [G-CSF] for neutropenia). The safety information is adequately described in Sarclisa Product Monograph. A Risk Management Plan (RMP) was assessed and considered acceptable by Health Canada, which provides measures for risk monitoring and mitigation in the post-market setting.

Overall, the benefit and risk profile of Sarclisa in combination with pomalidomide and dexamethasone is positive for the treatment of patients with relapsed and refractory multiple myeloma who have received at least two prior therapies including lenalidomide and dexamethasone.