New data from two clinical studies of the investigational use of isatuximab (Sarclisa®; Sanofi) administered subcutaneously (SC) via an on-body injector (OBI; also referred to as an on-body delivery system) in relapsed or refractory multiple myeloma support the potential use of this innovative delivery method to advance patient care, while upholding isatuximab’s efficacy and safety profile.
This is the conclusion of study results presented at the annual meeting of the American Society of Clinical Oncology (ASCO), held May 30-June 3, 2025 in Chicago, Illinois and simultaneously published in the Journal of Clinical Oncology. [1]
The presented data include full data from the IRAKLIA study (NCT05405166) the first randomized, open-label, pivotal phase 3 study to incorporate the use of an OBI in the treatment of MM, and demonstrate non-inferior efficacy and pharmacokinetics of isatuximab administered at a fixed dose SC via an OBI versus weight-based dosed isatuximab IV in combination with Pd in adult patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy. compared to isatuximab intravenous (IV) infusion.
“Our subcutaneous clinical program is rooted in our mission to address patient needs and reduce treatment burden in multiple myeloma,” noted Alyssa Johnsen, MD, Ph.D.,Global Therapeutic Area Head, Immunology and Oncology Development.
“We believe the novel on-body injector represents a significant innovation that could improve and streamline the treatment process for both patients and providers. We are pleased to share these data, the first to evaluate an on-body injector with a multiple myeloma treatment, and look forward to potentially bringing this formulation and administration option to the multiple myeloma community,” Johnsen added.
The OBI offers the potential to improve the overall patient experience in multiple myeloma treatment. Recent studies and surveys suggest the use of an OBI may be associated with greater convenience, flexibility, and patient satisfaction compared to IV or manual SC administration methods. [1]
In addition, an OBI may also streamline the administration process for providers, potentially reducing the physical burden on nurses and enabling them to possibly move freely through the use of a hands-free device while monitoring the patient during injection.
The updated data from the IRAKLIA and the IZALCO studies presented at ASCO were conducted using Enable Injections’ enFuse® hands-free OBI, an automated injector designed to subcutaneously administer high-volume medicines beginning with the click of a button, to administer the hyaluronidase-free SC formulation of isatuximab. The enFuse device uses a 30 gauge, hidden, and retractable needle that is smaller compared to some of the commonly used large-volume SC injection needles, which may support patient comfort.
Primary endpoints (IRAKLIA)
- Objective response rate (ORR) with isatuximab SC-Pd was 71.1% compared to 70.5% with Sarclisa IV-Pd, establishing non-inferiority (risk ratio [RR] 1.008; 95% confidence interval [CI]: 0.903-1.126; p=0.0006).
- Observed isatuximab mean (standard deviation [SD]) concentration before dosing (C trough) at steady state (C6D1 pre-dose) with isatuximab SC-Pd was 499 (259) ug/mL compared to 341 (169) ug/mL with Sarclisa IV-Pd, establishing non-inferiority (geometric mean ratio [GMR] 1.532; 90% CI: 1.316-1.784).
Secondary endpoints (IRAKLIA)
- Very good partial response (VGPR) or better rates were consistent between Sarclisa SC-Pd and isatuximab IV-Pd at 46.4% and 45.9%, respectively (RR 1.011; 95% CI: 0.841-1.215; p<0.0001).
- Observed isatuximab mean (SD) C trough at 4 weeks (C2D1 pre-dose) with Sarclisa SC-Pd was 421 (215) ug/mL compared to 302 (117) ug/mL with isatuximab IV-Pd (GMR 1.302; 90% CI 1.158-1.465).
- Systemic infusion reactions (IR) were significantly lower with isatuximab SC-Pd, occurring in only 1.5% of patients compared to 25% of those treated with isatuximab IV-Pd (RR: 0.061; 95% CI: 0.022-0.164; p<0.0001). Of note, nearly all IRs occurring were grade 1 or 2 and resolved within one day. No patients in the isatuximab SC-Pd arm discontinued treatment due to a systemic IR.
- Most isatuximab SC-Pd-treated patients (70%) reported being satisfied or very satisfied with their injection compared to 53.4% in the isatuximab IV-Pd arm, demonstrating the positive impact of this innovative method of administration on the patient experience (OR 2.036; 95% CI: 1.425-2.908; p=0.0001).
- 99.9% of isatuximab SC OBI injections were successfully delivered with no significant safety concerns related to the OBI.
- Progression-free survival (PFS) rates at 12 months were also similar, reaching 66.1% for patients treated with isatuximab SC-Pd compared to 65.1% of patients treated with isatuximab IV-Pd (HR 0.985; 95% CI: 0.726-1.338).
Overall safety
The overall safety profile of isatuximab SC-Pd observed in this study was consistent with the established safety profile of isatuximab IV-Pd, but with a notably lower rate of systemic IRs. No new safety concerns were observed, except for low-grade local injection site reactions (ISRs) associated with SC administration that occurred with a low incidence (0.4%, n=19/5,145 injections). Nearly all ISRs were grade 1, except for one episode of grade 2.
“Results from the IRAKLIA phase 3 study represent a potentially transformational advancement in the administration of multiple myeloma treatment. These data not only establish non-inferiority between isatuximab administered both subcutaneously and intravenously across several key endpoints but reinforce the positive impact that this on-body injector could have on the patient treatment experience, as demonstrated by patient satisfaction scores,” explained Xavier Leleu, MD, Ph.D.,Head of the Department of Hematology and Myeloma Clinic at the Hôpital La Mileterie and study investigator
IZALCO phase 2 study
In addition to the IRAKLIA phase 3 study, new data from the randomized, sequential, open-label, IZALCO phase 2 study were also presented. This study evaluated the efficacy and safety of isatuximab SC administered via manual push or an OBI, in combination with carfilzomib (Kyprolis®; Amgen) and dexamethasone (Decadron®; Merck & Co/MSD) (Kd) in adult patients with R/R MM who have received one to three prior lines of therapy. At a median follow-up of 10.1 months, the study demonstrated:
- ORR was 79.7% in patients treated with isatuximab SC-Kd (95% CI: 68.8-88.2) validating the prespecified efficacy hypothesis.
- With a median follow-up of 10 months, VGPR or better rate in patients treated with isatuximab SC-Kd was 62.2% and complete response (CR) or better rate was 21.6%.
- Only two patients treated with isatuximab SC-Kd, or 2.7% of recipients, experienced a grade 2 or lower IR event with manual injection and no IR event occurred with OBI administration; approximately 1% of injections were associated with a local ISR.
- After treatment with both methods, most patients (74.5%) preferred the OBI versus 17% who preferred manual injection and 8.5% with no preference (p=0.0004; binomial test against the null hypothesis of ≤50% rate).
The overall safety profile of isatuximab SC-Kd observed in this study was consistent with the established safety profile of isatuximab IV-Kd, with no new safety concerns observed.
Advancing patient and provider-centric innovation
While SC administration is currently available for certain multiple myeloma treatment regimens through a manual injection, administering large-volume medicines manually can present significant challenges, including a labor-intensive process for nurses, risk of strain and needlestick injuries, and potential need for larger needles that may compromise patient comfort and increase anxiety
“We believe multiple myeloma patients deserve a more convenient and comfortable treatment experience and recognize the crucial role providers play in delivering that care. Through our collaboration with Sanofi, we’ve aspired to advance an on-body injector that could transform the treatment experience for patients and providers alike,” said Mehul Desai, PharmD, MBA, Vice President, Medical Affairs, Enable Injections
“The results from the IRAKLIA and IZALCO studies represent a significant step toward our ambition and validate the potential of the on-body injector to deliver the same high standard of efficacy established with intravenous isatuximab,” noted Desai, concluded.
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Clinical trials
SC Versus IV Isatuximab in Combination With Pomalidomide and Dexamethasone in RRMM (IRAKLIA) – ClinicalTrials.gov ID NCT05405166
Highlights of prescribing information
Isatuximab (Sarclisa®; Sanofi)[Prescribing information]
Carfilzomib (Kyprolis®; Amgen)[Prescribing Information]
Dexamethasone (Decadron®; Merck & Co/MSD) [Prescribing Information]
Reference
[1] Ailawadhi S, Špička I, Spencer A, Lu J, Oriol A, Ling S, Schjesvold F, Berkovits A, Hus M, Li C, Dimopoulos MA, Rajnics P, Beşışık SK, Hungria V, Del Rosario Custidiano M, Parmar G, Leleu X, Li F, Cerchione C, Gomez C, Ishida T, Mateos MV, Buck TT, LeBlanc R, Minařík J, Goldschmidt H, Zhang R, Sémiond D, Suzan F, Stefanova-Urena M, Koch V, Moreau P. Isatuximab Subcutaneous by On-Body Delivery System vs Isatuximab Intravenous Plus Pomalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma: Phase 3 IRAKLIA Study.Journal of Clinical Oncology J(CO) 0, 10.1200/JCO-25-00744 DOI:10.1200/JCO-25-00744
Featured Image: Chicago Riverwalk, Chicago, IL, USA – Use under the Unsplash License
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