Regulatory Decision Summary for Darzalex SC
Review decision
The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.
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What was the purpose of this submission?
The purpose of this supplemental New Drug Submission was to seek the authorization of a new indication for Darzalex SC in combination with pomalidomide and dexamethasone for the treatment of relapsed/refractory multiple myeloma. After evaluation of the submission, Health Canada authorized Darzalex SC for the following indication:
- Darzalex SC (daratumumab injection) is indicated in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior line of therapy, including lenalidomide and a proteasome inhibitor.
Darzalex SC has previously received Notices of Compliance for several other indications in multiple myeloma as per the Darzalex SC Product Monograph. The product monograph is available from Health Canada’s Drug Product Database.
Why was the decision issued?
Authorization was based on one phase 3, randomized, open-label, multi-center, active controlled trial. Patients (n = 304) with relapsed or refractory multiple myeloma who had received at least one prior therapy and had received both lenalidomide and a proteasome inhibitor were randomized to either Darzalex SC in combination with pomalidomide and dexamethasone (DPd, n = 151) or pomalidomide and dexamethasone (Pd, n = 153).
The primary efficacy endpoint was progression free survival (PFS) as determined by validated computerized algorithm that applied the International Myeloma Working Group criteria. The study demonstrated a statistically significant and clinically meaningful benefit in PFS. The sponsor also demonstrated improvements in the overall response rate (ORR), very good partial response (VGPR) or better rate, the complete response (CR) or better rate, and the rate of minimal residual disease (MRD) negativity.
Treatment Emergent Adverse Events (TEAE) occurred in the majority of subjects in both treatment arms. The most common adverse events that were experienced with greater frequency in the DPd arm compared to the Pd arm were neutropenia, leukopenia, upper respiratory tract infection, asthenia, diarrhea, pneumonia, pyrexia, lymphopenia, and peripheral edema. The most common grade 3 - 4 adverse events that occurred more frequently in the DPd arm than the Pd arm were neutropenia, leukopenia, pneumonia, lymphopenia and febrile neutropenia. Overall, the safety findings were consistent with previous observations in clinical trials involving Darzalex SC.
The benefits observed outweigh the risks posed by Darzalex SC administered in combination with pomalidomide and dexamethasone. The benefit-risk balance is favourable.
The recommended dose of Darzalex SC is 1800 mg, administered subcutaneously, on days 1, 8, 15 and 22 for 2 cycles (each 28 days in length), then on days 1 and 15 (cycles 3 - 6), then on day 1 of every 28 day cycle until disease progression or unacceptable toxicity.
Decision issued
Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations