Regulatory Decision Summary for Darzalex SC

The purpose of this Supplement to a New Drug Submission (SNDS) was to seek authorization for a new indication for Darzalex SC in combination with bortezomib, lenalidomide, and dexamethasone, followed by maintenance treatment in combination with lenalidomide, for the treatment of patients with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplant. After evaluation of the submitted data package, Health Canada authorized Darzalex SC for the following indication:

• Darzalex SC is indicated in combination with bortezomib, lenalidomide, and dexamethasone, followed by maintenance treatment in combination with lenalidomide, for the treatment of adult patients with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplant.

This submission was filed under the Priority Review Policy.

Darzalex SC has previously been authorized for several other indications in multiple myeloma. Refer to the Darzalex SC Product Monograph for additional information.

Authorization was based on the results of a phase 3, randomized, open-label, multicenter study, MMY3014 (PERSEUS). Adult patients (n = 709) with newly diagnosed multiple myeloma who were eligible for autologous stem cell transplant (ASCT) were randomized 1:1 to receive either Darzalex SC (subcutaneous formulation) with bortezomib, lenalidomide, and dexamethasone (D-VRd, n = 355) or bortezomib, lenalidomide, and dexamethasone (VRd, n = 354).

The primary endpoint was progress-free survival (PFS) assessed by International Myeloma Working Group (IMWG) criteria. The study demonstrated a statistically significant and clinically meaningful improvement in PFS in the Darzalex SC arm compared to the control arm. Patients treated with Darzalex SC had a 58% reduction in the risk of experiencing a progression event. The study also demonstrated improvements in the overall complete response (CR) or better rate and overall minimal residual disease (MRD) negativity rate.

Nearly all patients in both treatment arms experienced treatment-emergent adverse events (TEAEs). The most common adverse events reported in at least 40% of patients were neutropenia, thrombocytopenia, diarrhea, and peripheral sensory neuropathy. The overall incidence rate of Grade 3 or 4 TEAEs was higher in the D-VRd arm than the VRd arm. The most common Grade 3 or 4 TEAEs with a ≥5% higher frequency in the D-VRd arm compared with the VRd arm were neutropenia and thrombocytopenia. Overall, the safety results were consistent with previous observations in other clinical trials with Darzalex SC.

Based on the evidence reviewed, the benefit of adding Darzalex SC to bortezomib, lenalidomide, and dexamethasone outweighs the risk and the benefit/risk profile is considered favourable for the treatment of adult patients with newly diagnosed multiple myeloma who are eligible for ASCT.

The recommended dose of Darzalex SC is 1,800 mg, administered subcutaneously, weekly for 8 weeks, followed by every two weeks from weeks 9 to 16. Treatment is stopped for high dose chemotherapy and ASCT then resumed for consolidation therapy, where Darzalex SC is administered every two weeks for 8 weeks. For maintenance therapy, Darzalex is administered very 4 weeks until disease progression, or discontinued for patients who have achieved MRD negativity that is sustained for 12 months and have been treated on maintenance for at least 24 months. Refer to the Product Monograph for details.

Overall, the benefit-harm-uncertainty profile was favourable for Darzalex SC (1,800 mg/15 mL) for the approved indication when used under the conditions of use recommended in the approved Product Monograph. Therefore, a Notice of Compliance (NOC) was recommended.

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

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

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