CHMP Recommends SC Isatuximab Via On-Body Injector for Multiple Myeloma

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending the approval of subcutaneous (SC) isatuximab (Sarclisa) in combination with approved standard-of-care (SOC) regimens for the treatment of patients with multiple myeloma, covering all currently European Union–approved indications for the intravenous (IV) formulation of the anti-CD38 monoclonal antibody.¹

A final decision on approval from the European Commission is anticipated in the coming months. If approved, isatuximab would represent the first anticancer treatment to be administered through both an on-body injector (OBI) and manual injection.

“This positive CHMP opinion is a pivotal milestone in our mission to improve the treatment experience for [patients with] multiple myeloma and [their] providers,” Olivier Nataf, global head of Oncology at Sanofi, stated in a news release. “Our aim is to evolve the treatment experience by combining the clinically proven efficacy of [isatuximab] with innovative subcutaneous delivery via an OBI. This advancement reflects our unwavering commitment to patients and dedication to transforming care in ways that truly matter to people living with cancer.”

The EMA’s CHMP recommendation was supported by data from the phase 3 IRAKLIA trial (NCT05405166), where the SC formulation demonstrated noninferiority to IV isatuximab in patients with relapsed/refractory multiple myeloma. Findings presented at the 2025 ASCO Annual Meeting demonstrated that patients treated with SC isatuximab via OBI in combination with pomalidomide (Pomalyst) and dexamethasone (Pd; n = 263) experienced an overall response rate (ORR) of 71.1% compared with 70.5% for patients treated with IV isatuximab plus Pd (n = 268; relative risk [RR], 1.008; 95% CI, 0.903-1.126; P = .0006), meeting a coprimary end point. The stringent complete response (sCR) plus CR rates were 17.9% for the SC formulation vs 20.5% for the IV formulation. Notably, the very good partial response (VGPR) or better rate was 46.4% in the OBI arm vs 45.9% in the IV arm (RR, 1.011; 95% CI, 0.841-1.215; P < .0001).

The trial also met its other coprimary end point, with SC isatuximab demonstrating noninferiority to the IV formulation regarding C_trough of isatuximab at steady state at cycle 6, day 1 (geometric mean ratio, 1.532; 90% CI, 1.316-1.784).

How was the IRAKLIA trial designed?

The international, randomized, open-label, noninferiority study enrolled patients at least 18 years of age with relapsed/refractory multiple myeloma who had received at least 1 prior line of therapy.

Patients were randomly assigned 1:1 between the SC and IV arms, with key stratification factors including multiple myeloma isotype, body weight, and number of prior lines of therapy. Patients in the SC arm received isatuximab at 1400 mg via OBI on days 1, 8, 15, and 22 of the first 28-day cycle, then on days 1 and 15 of subsequent cycles. In the IV arm, the anti-CD38 monoclonal antibody was given at 10 mg/kg on the same schedule. Patients in both arms also received SOC Pd, with pomalidomide given at 4 mg per day on days 1 to 21 of each cycle and dexamethasone administered at 40 mg on days 1, 8, 15, and 22 of each cycle.

Along with the coprimary end points of ORR and cycle 6, day 1 C_trough, key secondary end points included VGPR or better rate; C_trough at cycle 2, day 1; the incidence of infusion reactions; and patient satisfaction.

What safety data were reported for SC isatuximab administered via OBI?

Findings showed that infusion reactions were reported in 1.5% of patients in the SC isatuximab arm (n = 263) vs 25.0% of patients in the IV arm (n = 264). Among 5145 total SC isatuximab injections given via OBI, local injection site reactions were reported in 0.4% of injections; of the 19 instances of local injection site reactions, 18 were grade 1, with 1 reported at grade 2. Notably, 78.9% of local injection site reactions occurred on the day of injection and resolved the same day.

Any-grade treatment-emergent adverse effects (TEAEs) were reported in 97.0% of patients in the SC arm vs 96.6% of patients in the IV arm. The rates of grade 3 or higher TEAEs were 81.7% and 76.1%, respectively; treatment-related grade 3 or higher TEAEs occurred at respective rates of 65.8% and 64.4%. Serious TEAEs were reported in 52.9% of patients in the SC group vs 48.1% of patients in the IV group; the respective rates of treatment-related serious TEAEs were 27.0% and 29.5%. OBI-related TEAEs were reported in 3.4% of patients in the experimental arm.

TEAEs led to full treatment discontinuation in 8.4% of patients in the SC isatuximab arm vs 8.7% of patients in the IV arm. Grade 5 TEAEs occurred at rates of 6.8% and 7.2%, respectively.

References

1. 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 March 27, 2026. https://www.sanofi.com/en/media-room/press-releases/2026/2026-03-27-12-00-00-3263711
2. 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