On July 9, the U.S. Food and Drug Administration (FDA) approved the anti-CD38 monoclonal antibody isatuximab-irfc (Sarclisa Escena) for subcutaneous injection for multiple myeloma indications.
The specific indications approved for isatuximab are:
- In combination with pomalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor
- In combination with carfilzomib and dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy
- In combination with bortezomib, lenalidomide, and dexamethasone for the treatment of adult patients with newly diagnosed multiple myeloma who are not eligible for an autologous stem cell transplant.
IRAKLIA, IZALCO, and IsaSocut Trials
Efficacy of isatuximab administered subcutaneously in combination with pomalidomide and dexamethasone was evaluated in an open-label noninferiority trial, IRAKLIA (ClinicalTrials.gov identifier NCT05405166), which randomly assigned 531 patients 1:1 to receive either isatuximab administered subcutaneously with the on-body delivery system (OBDS) or intravenous isatuximab in combination with pomalidomide and dexamethasone. The major outcome measures were overall response rate as assessed by an Independent Review Committee (IRC) and the pharmacokinetic endpoint of Ctrough at steady state (corresponding to predose at cycle 6 day 1). The overall response rate was 71.1% (95% confidence interval [CI] = 65.2%–76.5%) in the subcutaneous arm and 70.5% (95% CI = 64.7%–75.9%) in the intravenous arm. The subcutaneous/intravenous geometric mean ratio (90% CI) for observed steady state Ctrough (predose at cycle 6 day 1) was 1.53 (90% CI = 1.32–1.78).
Efficacy of isatuximab administered subcutaneously in combination with carfilzomib and dexamethasone was evaluated in IZALCO (NCT05704049), in 74 patients in a phase II clinical study in patients with relapsed and/or refractory multiple myeloma. The efficacy outcome measure, overall response rate by IRC, was 79.7% (95% CI = 68.8%–88.2%).
Efficacy of isatuximab administered subcutaneously in combination with bortezomib, lenalidomide, and dexamethasone was evaluated in 74 patients in IsaSocut (NCT05889221), a single-arm, investigator-sponsored phase II clinical study in patients with newly diagnosed multiple myeloma who were not eligible for stem cell transplantation. The efficacy outcome measure, overall response rate, was 97.3% (95% CI = 90.6%–99.7%).
The prescribing information includes warnings and precautions for hypersensitivity and other administration reactions, neutropenia, infections, secondary primary malignancies, laboratory test interference, and embryo-fetal toxicity.
Recommended Dosage
The recommended isatuximab dose is 1,400 mg administered as a subcutaneous injection with the CirCLIQ OBDS or with a syringe and infusion set for manual administration, in combination with the specified regimens.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. Isatuximab received Orphan Drug designation.
