FDA Approves Subcutaneous Isatuximab Delivered Via On-Body Delivery System for Multiple Myeloma

The FDA has approved isatuximab-irfc (Sarclisa Escena) for subcutaneous injection for multiple myeloma indications.

Subcutaneous isatuximab can be administered as a subcutaneous injection with the CirCLIQ on-body delivery system (OBDS) or with a syringe and infusion set for manual administration, in combination with the specified regimens.

Subcutaneous isatuximab is indicated:

• in combination with pomalidomide (Pomalyst) 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 (Kyprolis) 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 (Velcade), lenalidomide (Revlimid), and dexamethasone for the treatment of adult patients with newly diagnosed multiple myeloma who are not eligible for an autologous stem cell transplant.

Data from the phase 3 IRAKLIA trial (NCT05405166) supported the approval, demonstrating that subcutaneous isatuximab delivered via OBDS generated noninferior efficacy and pharmacokinetic outcomes compared with the IV formulation in patients with relapsed/refractory multiple who had received at least 1 prior line of therapy.²

Patients in the subcutaneous arm (n = 263) experienced an overall response rate (ORR) of 71.1% compared with 70.5% for patients in the IV arm (n = 268), meeting one of the study's coprimary end points (relative risk [RR], 1.008; 95% CI, 0.903-1.126; P = .0006). The very good partial response (VGPR) or better rates were 46.4% and 45.9%, respectively (RR, 1.011; 95% CI, 0.841-1.125; P < .0001).

The study also met its other coprimary end point, with subcutaneous isatuximab demonstrating noninferiority to the IV formulation in C_trough at steady state on day 1 of cycle 6 (geometric mean ratio, 1.532; 90% CI, 1.316-1.784).²

How does the OBDS deliver subcutaneous isatuximab?

The OBDS is a sterile, single-use, user-filled, wearable injector. The device delivers a flat dose of 1400 mg with no adjustments needed for body weight. The needle remains hidden from the patient before, during, and after administration. No hyaluronidase is used within the subcutaneous formulation of isatuximab in the OBDS, and the flow rate is individualized based on subcutaneous interstitial pressure.

Subcutaneous isatuximab delivered via OBDS also received approval in the European Union in June 2026, covering all currently approved indications for the IV formulation.³

How was the IRAKLIA study designed?

The phase 3, randomized, international, open-label, noninferiority study enrolled patients at least 18 years of age with relapsed/refractory multiple myeloma who had received at least 1 prior line of therapy.² Patients were randomly assigned 1:1 and stratified by myeloma isotype, body weight, and number of prior lines of therapy.

In cycle 1, patients received subcutaneous isatuximab at 1400 mg on days 1, 8, 15, and 22 in combination with pomalidomide (Pomalyst) and dexamethasone (Pd); or IV isatuximab at 10 mg/kg on the same schedule in combination with Pd. In cycle 2 and beyond, isatuximab was administered subcutaneously at 1400 mg or via IV at 10 mg/kg on days 1 and 15 of each cycle, in combination with Pd. Treatment in both arms continued until progressive disease, unacceptable toxicity, or patient withdrawal.

The coprimary end points were ORR and C_trough at cycle 6, day 1. Secondary end points comprised VGPR or better rate; C_trough at cycle 2, day 1; incidence of infusion-related reactions (IRRs); and patient satisfaction.

What was reported regarding the safety of subcutaneous isatuximab delivered via OBDS?

Infusion-related reactions were reported in 1.5% of patients in the subcutaneous arm (n = 263) compared with 25.0% of patients in the IV arm (n = 264; RR, 0.061; 95% CI, 0.022-0.164).

Any-grade treatment-emergent adverse effects (TEAEs) occurred in 97.0% of patients in the subcutaneous arm vs 96.6% of patients in the IV arm. The respective rates of grade 3 or higher TEAEs were 81.7% and 76.1%. Drug-related TEAEs of grade 3 or higher were reported in 65.8% and 64.4% of patients, respectively. Serious TEAEs were experienced by 52.9% of patients in the subcutaneous arm vs 48.1% of patients in the IV arm; the respective rates of drug-related serious TEAEs were 27.0% and 29.5%. Grade 5 TEAEs were reported in 6.8% of patients in the subcutaneous arm compared with 7.2% of patients in the IV arm.

TEAEs leading to permanent, full treatment discontinuation occurred in 8.4% of patients in the subcutaneous arm vs 8.7% of patients in the IV arm. No TEAEs led to the permanent, partial discontinuation of isatuximab in either arm; partial discontinuations of pomalidomide (3.4% vs 5.3%) and dexamethasone (4.9% vs 2.7%) were reported. OBDS-related TEAEs of any grade occurred in 3.4% of patients in the experimental arm.

References

1. FDA approves isatuximab-irfc for subcutaneous injection for multiple myeloma indications. FDA. July 9, 2026. Accessed July 10, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-isatuximab-irfc-subcutaneous-injection-multiple-myeloma-indications
2. Ailawadhi S, Spicka I, Lu J, et al. Isatuximab (isa) subcutaneous (SC) via an on-body delivery system (OBDS) vs isa intravenous (IV), plus pomalidomide and dexamethasone (Pd) in relapsed/refractory multiple myeloma (RRMM): results of the randomized, non-inferiority, phase 3 IRAKLIA study. J Clin Oncol. 2025;43(suppl 16):7506. doi:10.1200/JCO.2025.43.16_suppl.7506
3. Subcutaneous isatuximab administered via OBI approved in EU for multiple myeloma. OncLive. June 8, 2026. Accessed June 15, 2026. https://www.onclive.com/view/subcutaneous-isatuximab-administered-via-obi-approved-in-eu-for-multiple-myeloma