EC Approves Sanofi’s Subcutaneous Isatuximab for Multiple Myeloma Across All Existing Indications

The European Commission (EC) has approved isatuximab (Sarclisa) subcutaneous (SC) formulation from Sanofi for treating multiple myeloma (MM) across all indications currently approved for the intravenous (IV) formulation in the European Union (EU). Administered via Enable Injections' CirCLIQ on-body injector (OBI), isatuximab SC becomes the first anticancer therapy in the EU to be delivered through an OBI and the first MM treatment available by both SC OBI and manual SC injection, according to Sanofi.¹

The EC’s approval is supported by the pivotal IRAKLIA phase 3 study, which established non-inferiority of the SC formulation versus IV in relapsed/refractory (R/R) MM, and additional pharmacokinetic (PK) and patient preference data.

"The ability to administer a therapy through an on-body injector, particularly an anti-CD38 monoclonal antibody with well-established efficacy, either in the clinic or at home represents a meaningful step forward," said Mohamad Mohty, MD, PhD, professor of Hematology at Sorbonne University and head of the Clinical Hematology and Cellular Therapy Department at Saint-Antoine Hospital, Paris.

What did the IRAKLIA Phase 3 trial show regarding efficacy, safety, and patient experience?

IRAKLIA (NCT05405166) was a randomized, open-label phase 3 study evaluating SC isatuximab administered via OBI at a fixed dose versus weight-based IV isatuximab, each in combination with pomalidomide and dexamethasone (Pd), in adult patients with R/R MM who had received at least one prior line of therapy. Co-primary endpoints were objective response rate (ORR) assessed by independent review committee and isatuximab SC trough plasma concentration at steady state. ORR was 71.1% with isatuximab SC-Pd versus 70.5% with isatuximab IV-Pd, establishing non-inferiority (risk ratio: 1.008; 95% confidence interval [CI]: 0.903–1.126; p=0.0006).¹

The overall safety profile was consistent with the established IV profile. Systemic infusion reactions occurred in 25.0% of IV-treated patients versus 1.5% of SC OBI–treated patients. Local injection site reactions occurred in 0.4% of OBI injections (19 of 5,145), with nearly all grade 1. Grade ≥3 hematologic abnormalities included neutropenia (84.7% OBI vs. 74.3% IV), thrombocytopenia (26.1% vs. 23.0%), and anemia (17.6% vs. 19.5%). Among patients in countries permitting home administration, median injection duration was 13 minutes in both clinic and home settings, with no new safety signals in the at-home cohort.¹

What patient and healthcare provider preference data support the OBI administration approach?

A phase 2 study (IZALCO; NCT05704049) evaluated SC isatuximab administered via OBI or manual push in combination with carfilzomib and dexamethasone in R/R MM patients who had received one to three prior lines of therapy. Patient and healthcare provider preference were secondary objectives. After experiencing both methods, 74.5% of patients preferred OBI administration versus 17.0% who preferred manual injection and 8.5% with no preference (p=0.0004). In the IRAKLIA study, 70.0% of patients receiving SC via OBI reported being satisfied or very satisfied with their injection, compared with 53.4% of patients receiving IV isatuximab (OR: 2.036; 95% CI: 1.425–2.908; p=0.0001).

What is the clinical context, and what MM disease burden is driving demand for more flexible treatment delivery?

MM is an incurable plasma cell malignancy accounting for approximately 10% of hematologic cancers, with an estimated 176,000 new cases diagnosed globally each year.² Treatment typically involves prolonged, multi-agent regimens administered in repeated clinic cycles over months to years, imposing a logistical and physical burden on patients and caregivers and placing strain on healthcare system resources.³ Anti-CD38 monoclonal antibodies (mAbs), including isatuximab and daratumumab, have become foundational components of MM treatment across newly diagnosed and R/R settings, improving survival outcomes but requiring frequent clinical attendance when administered intravenously.⁴

What is isatuximab's mechanism of action and regulatory history in multiple myeloma?

Isatuximab is an immunoglobulin G1 mAb that targets a specific epitope on CD38, a surface glycoprotein highly expressed on MM cells, to mediate tumor cell killing through multiple immune effector mechanisms, including antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, and direct apoptosis induction.⁴ The IV formulation has been approved in approximately 60 countries across four indications encompassing transplant-eligible and transplant-ineligible newly diagnosed MM and R/R MM in combination with standard backbone regimens. Isatuximab IV has been prescribed to nearly 70,000 patients worldwide since its 2020 launch.¹ Regulatory submissions for the SC formulation are currently under review in the United States, China, and Japan, according to Sanofi.

What limitations apply to this approval, and what questions remain regarding real-world implementation?

The non-inferiority design of IRAKLIA was aimed at ORR and PK endpoints rather than progression-free or overall survival, and long-term outcome data comparing SC and IV formulations in routine clinical practice are not yet available. The neutropenia rate was higher in the OBI arm (84.7% vs. 74.3% grade ≥3), which suggests that monitoring in post-approval pharmacovigilance may be warranted.

Home administration data were generated in a subset of patients from countries with permissive home-infusion frameworks, and generalizability across EU healthcare systems with variable home care infrastructure may likely require real-world evaluation. US, Chinese, and Japanese regulatory decisions on the SC formulation remain pending.

References

1. Sanofi. Press Release: Sanofi’s Sarclisa subcutaneous approved in the EU as the first anticancer treatment administered via an on-body injector. Published June 8, 2026. Accessed June 9, 2026. https://www.sanofi.com/en/media-room/press-releases/2026/2026-06-08-05-00-00-3307781
2. Rajkumar SV. Multiple myeloma: 2022 update on diagnosis, risk stratification, and management. Am J Hematol. 2022;97(8):1086-1107. doi:10.1002/ajh.26590
3. Palumbo A, Anderson K. Multiple myeloma. N Engl J Med. 2011;364(11):1046-1060. doi:10.1056/NEJMra1011442
4. Martin TG, Corzo K, Chiron M, et al. Therapeutic opportunities with pharmacological inhibition of CD38 with isatuximab. Cells. 2019;8(12):1522. doi:10.3390/cells8121522