Subcutaneous Isatuximab Earns EU Approval in Multiple Myeloma

A subcutaneous formulation of isatuximab-irfc (Sarclisa) has received EU approval as a treatment for patients with multiple myeloma across all existing indications for the intravenous formulation of the agent, according to a news release from the developer, Sanofi.¹

Supporting data for the on-body injector (OBI) among this multiple myeloma population are derived from the phase 3 IRAKLIA trial (NCT05405166). Therein, the OBI displayed noninferior outcomes vs the intravenous solution, with respective objective response rates (ORRs) of 71.7% vs 70.5% (risk ratio [RR], 1.008; 95% CI, 0.903-1.126; P = .0006). Moreover, the overall safety profile of the OBI was consistent with the safety profile of the intravenous solution among adult patients with relapsed/refractory disease following 1 or more prior treatments.

In the subcutaneous arm of the study, 1.5% of patients experienced systemic infusion reactions compared with 25% of patients in the intravenous arm. Moreover, save for low-grade local injection site reactions occurring in 0.4% of OBI injections, no new safety concerns were identified with the subcutaneous formulation. One grade 2 injection site reaction was observed, and the remainder were grade 1.

The most common grade 3 or higher nonhematologic adverse effects (AEs) in the OBI and intravenous arms included pneumonia in 14.8% vs 15.5%, COVID-19 in 2.7% vs 1.9%, and upper respiratory tract infection in 1.5% of each arm, respectively. Regarding grade 3 or higher hematologic AEs, neutropenia (84.7% vs 74.3%), thrombocytopenia (26.1% vs 23%), and anemia (17.6% vs 19.5%), were the most common in each arm.

Additionally, 70% of patients in the subcutaneous arm of the study reported being satisfied or very satisfied with treatment vs 53.4% of those in the intravenous arm (OR, 2.036; 95% CI, 1.425-2.908; P = .0001). In the phase 2 IZALCO trial (NCT05704049), which also evaluated both manual injection and OBI modalities, 74.5% of patients preferred the latter, with 17% favoring the intravenous injection, and 8.5% having showed no preference (P = .0004).²

“Multiple myeloma is a complex disease that often requires repeated and prolonged clinic visits, placing a considerable burden on patients and those who support them. There has been a need for innovative approaches to ease this aspect of the treatment journey,” 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 in Paris, France, stated in the news release.¹ ”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. With this new option now approved, we have an opportunity to reduce pressure on health care systems while placing greater flexibility and convenience at the heart of patient-centered care.”

In the IRAKLIA study, patients were randomly assigned to a fixed dose of isatuximab delivered via OBI or at a weight-based intravenous dose in combination with standard therapy including pomalidomide (Pomalyst) and dexamethasone. Treatment consisted of 28-day cycles and continued in the absence of disease progression, unacceptable toxicity, or other discontinuation criteria met.³

The co-primary end points included ORR per 2016 International Myeloma Working Group criteria assessed by an independent review committee (IRC), as well as the mean subcutaneous concentration before dosing.

Moreover, in the IZALCO protocol, patients with relapsed/refractory disease who received 1 to 3 prior treatments were similarly assigned to OBI or intravenous formulations of isatuximab, with dexamethasone and carfilzomib (Kyprolis). The primary end point was IRC-assessed ORR. Secondary end points included patient and provider preferences for each isatuximab modality.

In March 2026, the European Medicine Agency’s Committee for Medicinal Products for Human Use gave a positive opinion on the subcutaneous formulation of isatuximab based on the IRAKLIA findings.⁴ Additionally, in April 2026, the FDA extended the review period for the biologics license application for subcutaneous isatuximab. An updated Prescription Drug User Fee Act date of July 23, 2026, was given.⁵

References

1. Sanofi’s Sarclisa subcutaneous approved in the EU as the first anticancer treatment administered via an on-body injector. News release. Sanofi. June 8, 2026. Accessed June 8, 2026. https://tinyurl.com/45hey9ct
2. Parmar G, Capra M, Seguro F, et al. Efficacy and safety of isatuximab subcutaneous plus carfilzomib and dexamethasone in patients with relapsed/refractory multiple myeloma: results of the phase 2 study IZALCO. Blood Cancer J. Published online December 27, 2025. doi:10.1038/s41408-025-01436-0
3. New Sarclisa subcutaneous formulation met co-primary endpoints in the IRAKLIA phase 3 study in multiple myeloma. News release. Sanofi. January 9, 2025. Accessed June 8, 2026. https://tinyurl.com/53shnb3k
4. 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 June 8, 2026. https://tinyurl.com/4e2v9xm6
5. Sanofi provides update on the regulatory submission for Sarclisa subcutaneous in the US. News release. Sanofi. April 22, 2026. Accessed June 8, 2026. https://tinyurl.com/32edwm4h