FDA Approves Subcutaneous Isatuximab for Multiple Myeloma

The FDA approved the subcutaneous (SC) administration of the anti-CD38 antibody isatuximab-irfc (Sarclisa) in multiple myeloma, based on noninferiority shown in the phase 3 IRAKLIA trial (NCT05405166).¹

The approval covers SC isatuximab (Sarclisa Escena) as both manual injection and via an on-body injector (OBI) in combination with standard-of-care therapies across approved indications for the intravenous (IV) version of isatuximab. This marks the first approval of an anticancer agent through an on-body injector.

The approved indications are: in combination with pomalidomide (Pomalyst) and dexamethasone after 1 prior line of therapy including lenalidomide (Revlimid) and a proteasome inhibitor, in combination with carfilzomib (Kyprolis) and dexamethasone in relapsed or refractory disease after 1 to 3 prior lines, and in combination with bortezomib (Velcade), lenalidomide, and dexamethasone in newly diagnosed transplant-ineligible multiple myeloma.

Supporting Evidence for Subcutaneous Injection

Isatuximab is an anti-CD38 monoclonal antibody previously approved to treat multiple myeloma by IV administration, initially dosed every week followed by extended dosing schedules. Daratumumab (Darzelex Faspro), another anti-CD38 monoclonal antibody, was approved as an SC formulation in May 2020.

SC isatuximab in combination with pomalidomide and dexamethasone demonstrated noninferiority in terms of efficacy and pharmacokinetics vs IV in patients with relapsed/refractory multiple myeloma in the multicenter open-label phase 3 IRAKLIA trial.² In the trial, 531 patients were randomly assigned 1:1 to receive the SC formulation or IV isatuximab. Those who received the SC formulation did so through the OBI, which enables greater practice efficiency due to the device’s automated injection process.

The trial had a pair of coprimary end points: overall response rate (ORR) with a noninferiority margin of 0.839, and isatuximab C_trough level at cycle 6, day 1 with a noninferiority margin of 0.8. The overall response rate was ORR was 71.1% for OBI vs 70.5% for IV, respectively, and the mean cycle 6, day 1 C_trough was 499 μg/mL vs 340 μg/mL; C_trough geometric mean ratio (90% CI) was 1.532 (range, 1.316 to 1.784), with the lower bounds exceeding the noninferiority threshold.

The grade 3 or higher adverse event rates were 81.7% for OBI vs 76.1% with IV, and infusion reaction incidence was dramatically lower with the OBI (1.5% vs 25.0% with IV), with injection site reactions from the OBI occurring at a rate of 0.4%, all grade 1 or 2. The investigators stated that the efficacy and safety were considered comparable to the results of the ICARIA-MM trial (NCT02990338) that led to the introduction of this triplet regimen.

Other studies also have investigated SC isatuximab: the phase 3 GMMG-HD8 study (NCT05804032) in transplant-eligible newly diagnosed multiple myeloma (NDMM), the phase 2 IZALCO study (NCT05704049) in the relapsed/refractory (R/R) setting, the phase 2 ISASCOUT study (NCT05889221) in transplant-ineligible NDMM, and a phase 1b study (NCT04045795) in the R/R setting.

On June 8, 2026, the European Commission granted approval to SC isatuximab across all indications based on the positive findings from IRAKLIA and other studies.³ “The ability to administer a therapy through an [OBI], particularly an anti-CD38 monoclonal antibody with well-established efficacy, either in the clinic or at home represents a meaningful step forward,” Mohamad Mohty, MD, PhD, Professor of Hematology at the Sorbonne University and Head of the Clinical Hematology and Cellular Therapy Department at the Saint-Antoine Hospital, Paris, France, stated in a news release. Mohty cited this as an opportunity to provide greater flexibility for patients and lower the burden on health systems.

REFERENCES

1. FDA approves isatuximab-irfc for subcutaneous injection for multiple myeloma indications. FDA. July 10, 2026. Accessed July 10, 2026. https://tinyurl.com/4xpwfa77

2. Ailawadhi S, Špička I, Spencer A, et al. Isatuximab subcutaneous by on-body injector versus isatuximab intravenous plus pomalidomide and dexamethasone in relapsed/refractory multiple myeloma: phase III IRAKLIA study. J Clin Oncol. 2025;43(22):2527-2537. doi:10.1200/JCO-25-00744

3. Sanofi’s Sarclisa subcutaneous approved in the EU as the first anticancer treatment administered via an on-body injector. Sanofi. June 8, 2026. Accessed June 9, 2026. https://tinyurl.com/43hh6nnk