General Information

Sarclisa (isatuximab-irfc) is a CD38-directed cytolytic antibody.

Sarclisa is specifically indicated for the following:

use in combination with pomalidomide and dexamethasone, for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least two prior therapies including lenalidomide and a proteasome inhibitor;

use in combination with carfilzomib and dexamethasone (Kd), for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM) who have received one to three prior lines of therapy

Sarclisa is supplied as a solution for intravenous infusion.

Administer the following pre-medications prior to Sarclisa infusion to reduce the risk and severity of infusion-related reactions. Administer the recommended pre-medication agents 15 to 60 minutes prior to starting a Sarclisa infusion.

Dexamethasone 40 mg orally or intravenously (or 20 mg orally or intravenously for patients ≥75 years of age).

Acetaminophen 650 mg to 1000 mg orally (or equivalent).

H2 antagonists.

Diphenhydramine 25 mg to 50 mg orally or intravenously (or equivalent). The intravenous route is preferred for at least the first 4 infusions

Sarclisa should be administered by a healthcare professional, with immediate access to emergency equipment and appropriate medical support to manage infusion-related reactions if they occur. The recommended dose of Sarclisa is 10 mg/kg actual body weight administered as an intravenous infusion in combination with pomalidomide and dexamethasone, according to the following schedule:

Cycle 1: Days 1, 8, 15, and 22 (weekly)

Cycle 2 and beyond: Days 1, 15 (every 2 weeks)

Each treatment cycle consists of a 28-day period. Treatment is repeated until disease progression or unacceptable toxicity.

Clinical Trial Results

The FDA approval of Sarclisa for use in combination with pomalidomide and dexamethasone was based on data from the Phase 3 trial, ICARIA-MM. The multicenter, multinational, randomized, open-label, 2-arm trial enrolled 307 patients with RRMM. The trial was designed to demonstrate the benefit of isatuximab in combination with pomalidomide and low-dose dexamethasone in the prolongation of Progression Free Survival (PFS) as compared to pomalidomide and low-dose dexamethasone. In the study, Sarclisa added to pom-dex (Sarclisa combination therapy) demonstrated a statistically significant improvement in progression free survival (PFS) with a median PFS of 11.53 months compared to 6.47 months with pom-dex alone. Sarclisa combination therapy also demonstrated a significantly greater overall response rate compared to pom-dex alone (60.4% vs. 35.3%).

The FDA approval of Sarclisa for use in combination with carfilzomib and dexamethasone (Kd), for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM) who have received one to three prior lines of therapy was based on data from the Phase 3 IKEMA study, a randomized, multi-center, open label clinical trial that enrolled 302 patients with relapsed multiple myeloma across 69 centers in 16 countries. In this study, Sarclisa added to Kd (Sarclisa combination therapy) reduced the risk of disease progression or death by 45% versus standard of care Kd alone. The median progression free survival (PFS) for Sarclisa combination therapy was not reached at the time of the pre-planned interim analysis. Secondary endpoints of the IKEMA trial assessed the overall response rate (ORR) for Sarclisa combination therapy compared to Kd, including complete response (CR) and very good partial response (VGPR). There was no statistically significant difference in ORR, which remained similar for each arm at 86.6% for the Sarclisa combination therapy versus 82.9% for Kd. The rate of CR was 39.7% in the Sarclisa combination therapy arm and 27.6% in the Kd arm. The rate of VGPR was 33% for patients receiving Sarclisa combination therapy and 28.5% for patients receiving Kd.2 At the time of the interim analysis, overall survival (OS) data were still immature.