FDA Approves Subcutaneous Isatuximab in Multiple Myeloma

The FDA has approved a subcutaneous formulation of isatuximab-irfc (Sarclisa Escena) in combination with standard-of-care regimens for patients with multiple myeloma across all currently approved indications for the agent’s intravenous formulation, according to a press release from the FDA.¹

The approved regimens are for isatuximab:

• in combination with pomalidomide (Pomalyst) and dexamethasone (Pd) in multiple myeloma after at least 1 prior line of therapy including lenalidomide (Revlimid) and a proteasome inhibitor.
• in combination with carfilzomib (Kyprolis) and dexamethasone (Kd) in relapsed/refractory multiple myeloma after 1 to 3 prior lines of therapy.
• in combination with bortezomib (Velcade), lenalidomide and dexamethasone (VRd) in newly diagnosed multiple myeloma not eligible for an autologous stem cell transplant.

What data supported subcutaneous isatuximab’s approval?

The agency based its decision on findings from the phase 3 IRAKLIA trial (NCT05405166), which demonstrated the noninferiority of subcutaneous isatuximab via on-body injector (OBI) vs weight-based intravenous therapy in combination with Pd in patients with previously treated relapsed/refractory multiple myeloma.

Previous findings from the IRAKLIA trial showed that 70% of patients in the subcutaneous therapy arm reported being satisfied or very satisfied with treatment compared with 53.4% of those in the intravenous arm (OR, 2.036; 95% CI, 1.425-2.908; P = .0001).² Additionally, the objective response rate (ORR) was 71.1% vs 70.5% in each respective arm, which showed noninferiority in the subcutaneous arm (risk ratio [RR], 1.008; 95% CI, 0.903-1.126; P = .0006).

The safety profile of subcutaneous isatuximab plus Pd in the IRAKLIA trial was comparable with the established profile of intravenous isatuximab-based therapy. Systemic infusion reactions were reported in 25% of the intravenous arm compared with 1.5% of the subcutaneous arm. Overall, investigators reported no new safety signals.

Additionally, investigators assessed the efficacy and safety of subcutaneous Kd among patients with relapsed/refractory multiple myeloma in the phase 2 IZALCO study (NCT05704049). Data showed that 74.5% of patients who experienced both administration methods preferred subcutaneous isatuximab administered via OBI vs manual injection, compared with 17% who preferred manual injection over OBI and 8.5% who showed no preference (P = .0004).

Isatuximab was also evaluated in combination with VRd in the phase 2 IsaSocut trial (NCT05889221). In the trial, the regimen demonstrated a 97.3% ORR (95% CI, 90.6%-99.7%) in 74 patients with newly diagnosed multiple myeloma who were not eligible for stem cell transplantation.

How did IRAKLIA and IZALCO work?

Patients in the IRAKLIA trial were randomly assigned to receive isatuximab subcutaneously or intravenously on days 1, 8, 15, and 22 of cycle 1, followed by day 1 and 15 of each subsequent 28-day cycle.³ Additionally, patients received pomalidomide orally on days 1 to 21 plus dexamethasone on days 1, 8, 15, and 22 of each cycle.

The trial’s primary end points included ORR per 2016 International Myeloma Working Group criteria and observed concentration before dosing of isatuximab at steady state. Secondary end points included very good partial response or better rate, infusion reactions, duration of response (DOR), time to first response, time to best response, progression-free survival (PFS), and overall survival (OS).

In the IZALCO trial, patients were assigned to receive subcutaneous isatuximab via manual or OBI administration in combination with Kd.⁴ The trial’s primary end points included ORR, maximum observed concentration, and cumulative area under the curve over the first 4 weeks of isatuximab therapy. Secondary end points included the incidence of infusion reactions, DOR, time to first response, time to best response, PFS, and OS.

What is the prescription information of isatuximab?

The recommended dose of isatuximab has been set at 1400 mg, administered as a subcutaneous injection with the CirCLIQ on-body delivery system or with a syringe and infusion set for manual administration, in combination with the approved regimens.

Warnings and precautions on the label were for hypersensitivity and other administration reactions, neutropenia, secondary primary malignancies, infections, embryo-fetal toxicity, and laboratory test interference.

What is isatuximab’s regulatory history?

The European Commission previously approved subcutaneous isatuximab plus standard-of-care therapy for patients with relapsed/refractory multiple myeloma in June 2026.² The approval was primarily based on findings from the IRAKLIA trial.

The FDA previously approved isatuximab in combination with bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (Isa-VRd) for patients with newly diagnosed multiple myeloma not eligible for autologous stem cell transplant in September 2024 based on data from the phase 3 IMROZ trial (NCT03319667).⁵ Additionally, isatuximab/Kd received FDA approval in March 2021 as a treatment for adults with relapsed/refractory multiple myeloma based on the phase 3 IKEMA trial (NCT03275285).⁶The FDA also approved isatuximab/Pd among patients with previously treated multiple myeloma in March 2020 based on findings from the phase 3 ICARIA-MM study (NCT02990338).⁷

References

1. FDA approves isatuximab-irfc for subcutaneous injection for multiple myeloma indications. News release. FDA. July 9, 2026. Accessed July 10, 2026. https://tinyurl.com/4cccdbpn
2. Sanofi’s Sarclisa subcutaneous approved in the EU as the first anticancer treatment administered via an on-body injector. News release. Sanofi. June 8, 2026. Accessed July 9, 2026. https://tinyurl.com/45hey9ct
3. SC versus IV isatuximab in combination with pomalidomide and dexamethasone in RRMM (IRAKLIA). ClincialTrials.gov. Updated November 14, 2025. Accessed July 9, 2026. https://tinyurl.com/j3sf5unv
4. A study to investigate subcutaneous isatuximab in combination with carfilzomib and dexamethasone in adult participants with relapsed and/​or refractory multiple myeloma (IZALCO). ClinicalTrials.gov. Updated December 29, 2025. Accessed July 9, 2026. https://tinyurl.com/2tawdvw3
5. FDA approves istauximab-irfc with bortezomib, lenalidomide, and dexamethasone for newly diagnosed multiple myeloma. FDA. News release. September 20, 2024. Accessed July 9, 2026. https://tinyurl.com/2p9n9ecc
6. FDA approves Sarclisa (isatuximab) in combination with carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma. News release. Sanofi. March 31, 2021. Accessed July 9, 2026. https://tinyurl.com/yc2wjyfv
7. Sanofi: FDA approves Sarclisa® (isatuximab-irfc) for patients with relapsed refractory multiple myeloma. News release. Sanofi. March 2, 2020. Accessed July 9, 2026. https://tinyurl.com/43wavnrb