Subcutaneous Isatuximab Gains Approval for MM in Japan Ahead of Anticipated FDA Decision

Subcutaneous (SC) isatuximab (Sarclisa; Sanofi) was approved in Japan for the treatment of multiple myeloma (MM), marking another regulatory milestone for the anti-CD38 monoclonal antibody as it awaits a decision from the FDA on a US application currently under review.¹

The Ministry of Health, Labour and Welfare in Japan approved the SC formulation in combination with pomalidomide (Pomalyst; Bristol Myers Squibb) and dexamethasone (Pd) or carfilzomib (Kyprolis; Onyx Pharmaceuticals, Inc) for patients with relapsed or refractory MM (R/R MM), as well as in combination with bortezomib (Velcade; Millennium Pharmaceuticals), lenalidomide (Revlimid; Celgene Corporation), and dexamethasone (VRd) for adults with newly diagnosed MM (NDMM).¹

This approval follows a recent authorization in the European Union and positions subcutaneous isatuximab for potential entry into another major market should the FDA grant approval later this year.¹

Although intravenous (IV) isatuximab is already approved across multiple MM treatment settings, the availability of a subcutaneous formulation could offer a more convenient administration option for patients and treatment centers. The approval of subcutaneous isatuximab in Japan is particularly notable because it positions the therapy to compete more directly with subcutaneous daratumumab (Darzalex Faspro; Janssen Biotech), another anti-CD38 monoclonal antibody used in multiple myeloma.

IRAKLIA Trial Supports Japanese Approval

The Japanese approval was supported by findings revealed in the phase 3 IRAKLIA trial (NCT05405166)², which evaluated subcutaneous isatuximab administered through an on-body injector (OBI) in combination with pomalidomide and dexamethasone compared with IV isatuximab plus pomalidomide and dexamethasone in adults with R/R MM who received at least 1 prior line of therapy. The randomized, open-label study was designed to determine whether the SC formulation could achieve efficacy and pharmacokinetic outcomes comparable to the IV formulation while potentially reducing treatment burden.^1,2

Findings revealed that treatment with SC isatuximab plus Pd achieved an objective response rate of approximately 71.1% compared with 70.5% among patients treated with IV isatuximab plus Pd, meeting the study's primary end point for noninferiority (risk ratio, 1.008 [95% CI, 0.903-1.126]; P = .0006).¹

The safety profile observed with SC administration was generally consistent with that observed with IV isatuximab. Infusion-related reactions occurred in approximately 25% of patients receiving IV isatuximab compared with 1.5% of patients treated with the SC formulation.¹

There were no new safety signals identified. Low-grade injection-site reactions occurred in 0.4% of OBI administrations, with nearly all events reported as grade 1. The most common grade 3 or higher nonhematologic adverse events included pneumonia, COVID-19 infedction, and upper respiratory tract infection, and the most common hematologic laboratory abnormalities included neutropenia, thrombocytopenia, and anemia.¹

Expert Highlights Patient and Pharmacy Implications

Matthew M. Lei, PharmD, BCOP, clinical pharmacy specialist at Massachusetts General Hospital, highlighted the potential patient-care and operational implications of the SC OBI. “Isatuximab SC OBI would represent another option for patients and was viewed more favorably from patient perspectives in the IRAKLIA and IZALCO studies,” Lei said in a statement to Pharmacy Times.

The hyaluronidase-free formulation is delivered as a 10-mL injection via a hands-free, battery-free device that adjusts the flow rate using a small amount of pressure, which Lei noted may help explain why study participants reported less discomfort compared with manual SC injection during clinical evaluation. He also emphasized that pharmacists would be central to implementation if the SC formulation receives FDA approval.

“Pharmacists will play an important role for facilitating access to isatuximab SC OBI if approved by the FDA,” he said. Pharmacists may need to help practices address storage, preparation, dispensing, formulary review, and treatment-plan updates while accounting for both the medication and its accompanying device. By replacing a manual SC push with hands-free administration, the platform may also reduce nursing administration time and create resource efficiencies for infusion pharmacies, according to Lei.

FDA Review Remains Ongoing

In addition to standard manual SC administration, the US application includes the CirCLIQ OBI platform.¹ If approved by the FDA, SC isatuximab would provide health care professionals with an additional anti-CD38 treatment option, potentially expanding the flexibility of therapy administration in multiple myeloma treatment.

REFERENCES

1. Sanofi. Sanofi’s Sarclisa subcutaneous formulation approved in Japan for patients with multiple myeloma. Press release. June 19, 2026. https://www.sanofi.com/en/media-room/press-releases/2026/2026-06-19-10-31-15-3314694

2. SC Versus IV Isatuximab in Combination With Pomalidomide and Dexamethasone in RRMM (IRAKLIA). ClinicalTrials.gov identifier: NCT05405166. Updated November 14, 2025. Accessed June 22, 2026. https://clinicaltrials.gov/study/NCT05405166