FDA Delays Decision on Subcutaneous Isatuximab in Multiple Myeloma

The FDA has extended the review period for a biologics license application (BLA) seeking approval for subcutaneous isatuximab-irfc (Sarclisa) plus standard-of-care regimens for patients with multiple myeloma across all current indications for which intravenous isatuximab is already approved, according to a press release from the developer, Sanofi.¹

The agency established a revised Prescription Drug User Fee Act date of July 23, 2026, for subcutaneous isatuximab in these indications. Subcutaneous isatuximab would become the first available anti-cancer therapeutic to be given via on-body injector (OBI) administration if approved.

In March 2026, the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion supporting the approval of subcutaneous isatuximab administered via OBI and manual injections among those with multiple myeloma.² The positive opinion was supported by findings from the phase 3 IRAKLIA study (NCT05405166), which highlighted the noninferiority of subcutaneous isatuximab vs the intravenous formulation among those with relapsed/refractory multiple myeloma.

Additional studies supporting the CHMP’s recommendation included:

• The phase 3 GMMG-HD8 study (NCT05804032) in transplant-eligible newly diagnosed multiple myeloma (NDMM)
• The phase 2 IZALCO trial (NCT05704049) in relapsed/refractory multiple myeloma
• The phase 2 ISASOCUT study (NCT05889221) in transplant-ineligible NDMM
• A phase 1b study (NCT04045795) among patients with relapsed/refractory multiple myeloma who received 2 or more prior lines of treatment

What were the efficacy and safety findings with subcutaneous isatuximab in the IRAKLIA study?

Findings presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting showed an objective response rate (ORR) of 71.1% with subcutaneous isatuximab plus pomalidomide (Pomalyst) and dexamethasone (Pd) vs 70.5% with intravenous isatuximab plus Pd, fulfilling the trial’s co-primary end point of non-inferiority for ORR (relative risk, 1.008; 95% CI, 0.903-1.126; P = .0006).³ Additionally, investigators noted that subcutaneous isatuximab showed non-inferiority for the co-primary end point of C_trough at steady state, with a lower CI of the geometric means ratio exceeding the non-inferiority margin of 0.8 (geometric mean ratio, 1.532; 90% CI, 1.316-1.784).

The safety profile of subcutaneous isatuximab was similar to that of the intravenous formulation, as investigators observed no new unexpected safety signals. Treatment-emergent adverse effects (TEAEs) of any grade occurred in 97.0% of the subcutaneous isatuximab arm vs 96.6% of the intravenous isatuximab arm; 81.7% and 76.1% of patients in each respective arm experienced grade 3 or higher TEAEs. Additionally, 3.4% of patients who received subcutaneous isatuximab had TEAEs associated with OBI delivery; none of these toxicities were serious.

“Results from the IRAKLIA phase 3 study represent a potentially transformational advancement in the administration of multiple myeloma treatment,” study investigator Xavier Leleu, MD, PhD, head of the Department of Hematology and Myeloma Clinic at the Hôpital La Mileterie, stated in a press release regarding these data from June 2025.⁴ “These data not only establish non-inferiority between [isatuximab] administered both subcutaneously and intravenously across several key end points but reinforce the positive impact that this [OBI] could have on the patient treatment experience, as demonstrated by patient satisfaction scores.”

How was IRAKLIA designed?

In the phase 3 IRAKLIA study, 531 patients 18 years and older with at least 1 prior line of therapy for relapsed/refractory multiple myeloma were randomly assigned 1:1 to receive isatuximab administered intravenously at 10 mg/kg (n = 268) or subcutaneously via OBI injection at 1400 mg (n = 263), in combination with pomalidomide and dexamethasone.

The trial’s co-primary end points were ORR and C_trough. Secondary end points included the very good partial response or better rate, infusion reaction incidence, and patient satisfaction.

References

1. Sanofi provides update on the regulatory submission for Sarclisa subcutaneous in the US. News release. Sanofi. April 22, 2026. Accessed April 23, 2026. https://tinyurl.com/32edwm4h
2. Sanofi’s Sarclisa subcutaneous formulation administered via on-body injector recommended for EU approval by the CHMP to treat multiple myeloma. News release. Sanofi. March 27, 2026. Accessed April 23, 2026. https://tinyurl.com/35cpa56e
3. 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
4. ASCO: new Sarclisa data support subcutaneous administration with on-body injector. News release. Sanofi. June 3, 2025. Accessed April 23, 2026. https://tinyurl.com/3ebpprf7