Japan Approves On-Body Injector for Subcutaneous Isatuximab in Multiple Myeloma

Japan's Ministry of Health, Labour and Welfare has approved the CirCLIQ Injector, which is based on the enFuse On-Body Delivery System, for the administration of subcutaneous isatuximab (Sarclisa) in patients with multiple myeloma.¹

This regulatory decision marks the first approval of an anticancer treatment delivered via an on-body injector in Japan.

In Japan, subcutaneous isatuximab is approved for use:

• in combination with pomalidomide (Pomalyst) and dexamethasone, or in combination with carfilzomib (Kyprolis), for the treatment of patients with relapsed/refractory multiple myeloma
• in combination with bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone for the treatment of adult patients with newly diagnosed multiple myeloma.

Subcutaneous isatuximab received approval in Japan in June 2026, and the October decision adds use of the on-body delivery system.^1,2 The subcutaneous approval was supported by data from the phase 3 IRAKLIA trial (NCT05405166), along with supporting studies that evaluated both manual subcutaneous administration and administration via the enFuse-based on-body injector.²

In IRAKLIA, subcutaneous isatuximab delivered via an on-body delivery system plus pomalidomide and dexamethasone produced an overall response rate (ORR) of 71.1% (n = 263) vs 70.5% with intravenous (IV) isatuximab plus pomalidomide and dexamethasone (n = 268), meeting the coprimary end point of noninferiority (relative risk [RR], 1.008; 95% CI, 0.903-1.126; P = .0006).^2,3 Rates of very good partial response or better were 46.4% and 45.9%, respectively (RR, 1.011; 95% CI, 0.841-1.125; P < .0001).³ The trial also met its other coprimary end point, with subcutaneous isatuximab demonstrating noninferiority to IV isatuximab in trough concentration (C_trough) at steady state on cycle 6, day 1 (geometric mean ratio, 1.532; 90% CI, 1.316-1.784).

"This approval is another important milestone in our mission to expand access to novel drug delivery solutions around the world," Michael D. Hooven, chairman and chief executive officer of Enable Injections, said in the news release.¹ "We're proud to partner with Sanofi to bring our enFuse technology to patients in Japan and to support an innovative treatment option for people living with multiple myeloma. As the adoption of subcutaneous delivery continues to grow globally, we're excited to help our pharmaceutical partners bring more therapies to patients."

The Japanese approval follows the July 2026 FDA approval of subcutaneous isatuximab-irfc (Sarclisa Escena) for administration with the CirCLIQ on-body delivery system or with a syringe and infusion set for manual administration, which made it the first anticancer therapy approved by the FDA for delivery via an on-body system.⁴ Subcutaneous isatuximab delivered via an on-body injector was approved in the European Union in June 2026, covering all approved indications for the IV formulation.⁵

How does the on-body injector deliver subcutaneous isatuximab?

Isatuximab is an anti-CD38 monoclonal antibody, and it is the only anti-CD38 monoclonal antibody for multiple myeloma that offers both on-body injector and manual subcutaneous administration.¹ The CirCLIQ Injector has a hidden, retractable needle that is shorter and thinner than needles commonly used for large-volume subcutaneous injections.

The device is a sterile, single-use, user-filled, wearable injector that delivers a flat dose of 1400 mg with no adjustment for body weight.⁴ The needle remains hidden from the patient before, during, and after administration. The subcutaneous formulation of isatuximab used in the device does not contain hyaluronidase, and the flow rate is individualized based on subcutaneous interstitial pressure.

How was the IRAKLIA trial designed?

The randomized, international, open-label, noninferiority phase 3 trial enrolled patients at least 18 years of age with relapsed/refractory multiple myeloma who had received at least 1 prior line of therapy.³

Patients were randomly assigned 1:1 and stratified by myeloma isotype, body weight, and number of prior lines of therapy. In cycle 1, patients received subcutaneous isatuximab at 1400 mg or IV isatuximab at 10 mg/kg on days 1, 8, 15, and 22, each in combination with pomalidomide and dexamethasone. In cycle 2 and beyond, isatuximab was given subcutaneously at 1400 mg or intravenously at 10 mg/kg on days 1 and 15 of each cycle with pomalidomide and dexamethasone. Treatment continued until disease progression, unacceptable toxicity, or patient withdrawal.

The coprimary end points were ORR and C_trough at cycle 6, day 1. Secondary end points included the rate of very good partial response or better, Ctrough at cycle 2, day 1, the incidence of infusion-related reactions (IRRs), and patient satisfaction.

What is the safety profile of subcutaneous isatuximab?

IRRs occurred in 1.5% of patients in the subcutaneous arm (n = 263) vs 25.0% of patients in the IV arm (n = 264; RR, 0.061; 95% CI, 0.022-0.164).

Any-grade treatment-emergent adverse effects (TEAEs) occurred in 97.0% of patients in the subcutaneous arm vs 96.6% of patients in the IV arm. Grade 3 or higher TEAEs were reported in 81.7% and 76.1% of patients, respectively, and drug-related grade 3 or higher TEAEs were reported in 65.8% and 64.4%. Serious TEAEs occurred in 52.9% vs 48.1% of patients, and drug-related serious TEAEs occurred in 27.0% vs 29.5%. Grade 5 TEAEs were reported in 6.8% of patients in the subcutaneous arm and 7.2% of patients in the IV arm.

TEAEs led to permanent, full treatment discontinuation in 8.4% of patients in the subcutaneous arm vs 8.7% of patients in the IV arm. Partial discontinuations of pomalidomide (3.4% vs 5.3%) and dexamethasone (4.9% vs 2.7%) were reported, and no TEAEs led to permanent, partial discontinuation of isatuximab in either arm. On-body delivery system–related TEAEs of any grade occurred in 3.4% of patients in the subcutaneous arm.

References

1. Enable Injections announces approval in Japan for CirCLIQ Injector based on enFuse On-Body Delivery System. News release. Enable Injections. October 19, 2026. Accessed October 19, 2026. https://www.globenewswire.com/news-release/2026/10/19/3383404/0/en/enable-injections-announces-approval-in-japan-for-circliq-injector-based-on-enfuse-on-body-delivery-system.html
2. Sanofi’s Sarclisa subcutaneous formulation approved in Japan for patients with multiple myeloma. News release. Sanofi. June 19, 2026. Accessed October 19, 2026. https://www.sanofi.com/en/media-room/press-releases/2026/2026-06-19-10-31-15-3314694
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. FDA approves isatuximab-irfc for subcutaneous injection for multiple myeloma indications. FDA. July 9, 2026. Accessed October 19, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-isatuximab-irfc-subcutaneous-injection-multiple-myeloma-indications

4. Wahner A. Subcutaneous isatuximab administered via OBI approved in EU for multiple myeloma. OncLive. June 8, 2026. Accessed October 19, 2026. https://www.onclive.com/view/subcutaneous-isatuximab-administered-via-obi-approved-in-eu-for-multiple-myeloma