Regulatory Decision Summary for Sarclisa

The purpose of this Supplement to a New Drug Submission (SNDS) was to obtain market authorization, pursuant to section C.08.004 of the Food and Drugs Regulations, for Sarclisa, filed by Sanofi-Aventis Canada Inc.

The purpose of the Supplement to a New Drug Submission (SNDS) was to seek a new indication for Sarclisa, in combination with bortezomib, lenalidomide, and dexamethasone, for the treatment of patients with newly diagnosed multiple myeloma who are not eligible for autologous stem cell transplant (ASCT) or with no intent for ASCT as initial therapy.

After evaluation of the submitted data package, Health Canada authorized Sarclisa for the following indication: Sarclisa (isatuximab for injection) is indicated in combination with bortezomib, lenalidomide, and dexamethasone, for the treatment of patients with newly diagnosed multiple myeloma who are not eligible for autologous stem cell transplant (ASCT).

The sponsor consented to information sharing between Health Canada and health technology assessment organizations as part of an aligned review pathway.

Authorization of Sarclisa for the treatment of patients with newly diagnosed multiple myeloma who are not eligible for autologous stem cell transplant (ASCT) was based on an international, multicentre, randomized, open-label, two-arm, Phase 3 clinical trial, IMROZ (EFC12522). Adult patients (n = 446) with newly diagnosed multiple myeloma and who were not eligible for ASCT were randomized 3:2 to receive either Sarclisa in combination with bortezomib, lenalidomide, and dexamethasone (Isa-VRd) or bortezomib, lenalidomide, and dexamethasone (VRd) for four induction cycles. Following induction, patients entered a continuous treatment phase until disease progression or the occurrence of unacceptable toxicity. During this phase, those in the Isa-VRd arm received Sarclisa in combination with lenalidomide and dexamethasone (Isa-Rd), while patients in the VRd arm continued treatment with lenalidomide and dexamethasone (Rd).

The primary efficacy measure was progression-free survival (PFS), assessed by an Independent Response Committee using the International Myeloma Working Group (IMWG) criteria. The study demonstrated a statistically significant improvement in PFS in the Sarclisa (Isa-VRd) arm compared to the VRd arm, with a hazard ratio (HR) of 0.596. This indicates a 40.4% reduction in the risk of disease progression or death for patients treated with Isa-VRd. The median PFS was not reached (NR) in the Isa-VRd arm, compared to 54.3 months in the VRd arm. Key secondary efficacy measures included the complete response (CR)/stringent complete response (sCR) rate and the rate of minimal residual disease (MRD)-negative CR. Both were significantly higher in the Isa-VRd arm versus the VRd arm: CR/sCR rate was 74.7% vs. 64.1%, and MRD-negative CR rate was 55.5% vs. 40.9%. These results were supportive of the primary efficacy results.

In the IMROZ study, the most common adverse reactions (occurring in ≥20% of patients) in the Isa-VRd arm included diarrhea, peripheral sensory neuropathy, pneumonia, cataract, constipation, fatigue, upper respiratory tract infections, peripheral edema, neutropenia, infusion-related reactions, insomnia, COVID-19, back pain, bronchitis, and asthenia. Serious adverse reactions were reported in 70.7% of patients receiving Isa-VRd, compared to 67.4% of those receiving VRd. The most frequent serious adverse reaction (occurring in ≥5% of patients) in the Isa-VRd arm was pneumonia, including COVID-19-related pneumonia. Second primary malignancies (SPMs) occurred more frequently in the Isa-VRd arm (16.0% vs. 8.8% in the VRd arm). Most SPMs were skin cancers, followed by solid tumours and hematological malignancies. Adverse reactions with a fatal outcome during treatment occurred in 11% of patients in the Isa-VRd arm and 5.5% of patients in the VRd arm. Fatal adverse reactions reported in ≥1% of patients receiving Isa-VRd included COVID-19 pneumonia and pneumonia.

Overall, the benefit-harm-uncertainty profile of Sarclisa, in combination with bortezomib, lenalidomide and dexamethasone, is considered favorable for the treatment of adult patients with newly diagnosed multiple myeloma who are not eligible for ASCT when used under the conditions of use recommended in the approved Product Monograph. Therefore, a Notice of Compliance (NOC) was recommended.

The recommended dose for the new indication is 10 mg/kg actual body weight administered as an intravenous infusion.

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

Risks have been communicated in the approved Product Monograph and will continue to be monitored post market as outlined in the Risk Management Plan, with routine and non-routine pharmacovigilance activities.

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

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