FDA Extends Review of Subcutaneous Isatuximab for Multiple Myeloma

The FDA’s target action date for the decision on the approval of the subcutaneous (SC) formulation of isatuximab-irfc (Sarclisa) in multiple myeloma has been extended for 3 months to July 23, 2026.¹

The FDA review of the biologics license application includes data on SC isatuximab as both manual injection and via an on-body injector (OBI) in combination with standard-of-care therapies across all approved indications for the intravenous (IV) version of isatuximab.

Supporting Evidence for Subcutaneous Injection

Isatuximab is an anti-CD37 monoclonal antibody with multiple indications to treat multiple myeloma. SC isatuximab in combination with pomalidomide (Pomalyst) and dexamethasone demonstrated noninferiority in terms of efficacy and pharmacokinetics vs IV in relapsed/refractory multiple myeloma in the phase 3 IRAKLIA trial (NCT05405166).² Patients received the SC formulation via OBI, which enables greater practice efficiency due to the device’s automated injection process.

The coprimary end points of the study were 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. In 531 patients randomly assigned to receive OBI or IV isatuximab, the overall response rate was ORR was 71.1% vs 70.5%, 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 comparable (81.7% vs 76.1%) and infusion reaction incidence was dramatically lower with the OBI (1.5% vs 25.0%, respectively), with injection site reactions from the OBI occurring at a rate of 0.4%, all grade 1 or 2. 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 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 ISASOCUT study (NCT05889221) in transplant-ineligible NDMM, and a phase 1b study (NCT04045795) in the R/R setting.

The favorable study outcomes and practical advantages of SC isatuximab led to a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use, recommending that the SC isatuximab be approved in all indications in the European Union.³ A final decision is expected later this year.

The FDA decision for the subcutaneous formulation. If approved, this would be the first anticancer treatment to be administered through an OBI.

REFERENCES

1. Sanofi provides update on the regulatory submission for Sarclisa subcutaneous in the US. News release. Sanofi. April 22, 2026. Accessed April 22, 2026. https://tinyurl.com/ysy4z54x

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 formulation administered via on-body injector recommended for EU approval by the CHMP to treat multiple myeloma. Sanofi. March 27, 2026. Accessed April 22, 2026. https://tinyurl.com/bdkhpkd3