isatuximab subcutaneous (SAR650984 SC) / Sanofi - LARVOL DELTA

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. (ASCO 2025) - P3 | "IRAKLIA met its co-primary endpoints, showing efficacy and pharmacokinetic NI between Isa SC vs IV + Pd. No new safety signal besides a low ISR incidence was observed, showing excellent Isa SC tolerability. Far fewer infusion reactions and higher pt satisfaction were also noted for SC vs IV."

Clinical • Head-to-Head • P3 data • Hematological Malignancies • Multiple Myeloma • Oncology

Efficacy and safety of isatuximab subcutaneous (SC) plus carfilzomib and dexamethasone (Isa-Kd) in patients with relapsed/refractory multiple myeloma (RRMM): Results of the phase 2 study IZALCO. (ASCO 2025) - P2 | "Results of a Phase 1b study demonstrated safety and efficacy of Isa SC administration via an on-body delivery system (OBDS; an investigational wearable injector), plus pomalidomide and dexamethasone in RRMM pts. The study met its primary endpoint, demonstrating efficacy and safety of Isa SC administration in combination with Kd, either by manual injection or OBDS. Our study findings are comparable to those reported in the Phase 3 study IKEMA with Isa IV. Pts expressed a clear preference for receiving Isa SC by an OBDS."

Clinical • P2 data • Hematological Malignancies • Multiple Myeloma • Oncology

Analysis of pharmacotherapeutic approaches for multiple myeloma and correlated renal and pulmonary impairments: a retrospective real-world registry study in the Greater Gulf Region (REPAIR Study). (PubMed, Front Oncol) - "The VRd regimen (Bortezomib, Lenalidomide, and Dexamethasone) was the most frequent first-line therapy among transplant-ineligible patients (40.2%) and the most common induction and consolidation regimen (43.9% and 66.7%, respectively) in transplant-eligible patients...DKd (Daratumumab, Carfilzomib, and Dexamethasone), KPd (Carfilzomib, Pomalidomide, and Dexamethasone), and PVd (Pomalidomide, Bortezomib, and Dexamethasone) were the most widely used second, third, and fourth treatment lines, respectively (16.6%, 9.2%, and 12.5%)...Additionally, isatuximab was incorporated into 80%, 15%, and 5% of the regimens administered as second-, third-, and fourth-line treatments, respectively. This study provides valuable insights into the real-world management and treatment choices for RRMM, including the utilization of SCT and novel therapies such as isatuximab."

Journal • Real-world evidence • Retrospective data • Hematological Malignancies • Multiple Myeloma • Oncology • Renal Disease • Transplantation

MULTICENTER PHASE 2 STUDY OF SUBCUTANEOUS ISATUXIMAB PLUS BORTEZOMIB, LENALIDOMIDE, AND DEXAMETHASONE (ISA SC-VRD) IN NEWLY DIAGNOSED TRANSPLANT-INELIGIBLE MULTIPLE MYELOMA (NDMM TI): RESULTS FROM ISASOCUT (IFM 2022-05) (EHA 2025) - "The ISASOCUT study met its primary endpoint, demonstrating consistent efficacy of isatuximab in NDMM TI patients, regardless of SC or IV administration. These results support Isa SC-VRd as a new SOC for NDMM TI, offering a longer but less dose-intensive induction regimen compared to IMROZ"

Clinical • P2 data • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

EFFICACY AND SAFETY OF ISATUXIMAB SUBCUTANEOUS (SC) PLUS CARFILZOMIB AND DEXAMETHASONE (ISA-KD) IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA (RRMM): RESULTS OF THE PHASE 2 STUDY IZALCO (EHA 2025) - P2 | "Results of a Phase 1b study demonstrated safety and efficacy of Isa SC administration via an on-body delivery system (OBDS; an investigational wearable injector), plus pomalidomide and dexamethasone in RRMM pts. The study met its primary endpoint, demonstrating efficacy and safety of Isa SC administration in combination with Kd, either by manual injection or OBDS. Our study findings are comparable to those reported in the Phase 3 study IKEMA with Isa IV. Pts expressed a clear preference for receiving Isa SC by an OBDS."

Clinical • P2 data • Hematological Malignancies • Multiple Myeloma • Oncology

ISATUXIMAB SUBCUTANEOUS VIA AN ON-BODY DELIVERY SYSTEM VERSUS ISATUXIMAB INTRAVENOUS, PLUS POMALIDOMIDE AND DEXAMETHASONE, IN RELAPSED/REFRACTORY MULTIPLE MYELOMA: THE RANDOMIZED PHASE 3 IRAKLIA STUDY (EHA 2025) - P3 | "IRAKLIA met its co-primary endpoints, showing efficacy and pharmacokinetic non-inferiority of Isa SC OBDS compared with Isa IV, plus Pd. No new safety signal besides a low ISR incidence was observed, showing excellent tolerability of Isa SC OBDS. Far fewer infusion reactions and a higher patient satisfaction were also noted for Isa SC OBDS compared with Isa IV."

Clinical • P3 data • Hematological Malignancies • Multiple Myeloma • Oncology

SubQSA: A Study to Investigate Subcutaneous Isatuximab in Combination With Weekly Carfilzomib and Dexamethasone in Adult Participants With Relapsed and/or Refractory Multiple Myeloma (clinicaltrials.gov) - P2 | N=64 | Recruiting | Sponsor: Sanofi | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Multiple Myeloma • Oncology

Lenalidomide, Bortezomib and Dexamethasone Induction Therapy with Either Intravenous or Subcutaneous Isatuximab in Patients with Newly Diagnosed Multiple Myeloma (clinicaltrials.gov) - P3 | N=514 | Active, not recruiting | Sponsor: University of Heidelberg Medical Center | Recruiting ➔ Active, not recruiting

Enrollment closed • Head-to-Head • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Minimal Residual Disease Significance in Multiple Myeloma Patients Treated with Anti-CD38 Monoclonal Antibodies. (PubMed, Pharmaceuticals (Basel)) - "This review analyzes updated results from recent clinical trials utilizing anti-CD38 monoclonal antibodies such as isatuximab and daratumumab in terms of their responses and MRD data. MRD-driven therapy appears promising for the future of MM patients, and emerging minimally invasive techniques to assess MRD are under investigation as novel potential methods to replace or integrate traditional MRD evaluation."

Journal • Minimal residual disease • Review • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology

ELISA in Relapsed/Refractory MM (clinicaltrials.gov) - P2 | N=30 | Not yet recruiting | Sponsor: Massachusetts General Hospital

New P2 trial • Hematological Malignancies • Multiple Myeloma • Oncology

Isatuximab subcutaneous: “GMMG-HD7 phase 3 study: transplant-eligible front-line patients 43% improvement in progression-free survival (PFS)”; Multiple myeloma (Sanofi) - Q4 & FY 2024 Results

P3 data • Hematological Malignancies • Multiple Myeloma • Oncology

Isatuximab subcutaneous: Regulatory submissions in US/EU for multiple myeloma (based on IRAKLIA trial) in H1 2025 (Sanofi) - Q4 & FY 2024 Results: Regulatory submissions in Japan/China for multiple myeloma (based on IRAKLIA trial) in H2 2025

China filing • EMA filing • FDA filing • Japan filing • Multiple Myeloma • Oncology

International Treatment-extension Study in Adult Participants With Multiple Myeloma and Who Have Derived Clinical Benefit From Isatuximab (clinicaltrials.gov) - P2 | N=70 | Active, not recruiting | Sponsor: Sanofi | Recruiting ➔ Active, not recruiting

Enrollment closed • Hematological Malignancies • Multiple Myeloma • Oncology

Press Release: New Sarclisa subcutaneous formulation met co-primary endpoints in the IRAKLIA phase 3 study in multiple myeloma (GlobeNewswire) - P3 | N=531 | IRAKLIA (NCT05405166) | Sponsor: Sanofi | "Results from the investigational, randomized, open-label IRAKLIA phase 3 study demonstrated that Sarclisa administered at a fixed dose subcutaneously (SC) via an on-body delivery system (OBDS) in combination with pomalidomide and dexamethasone (Pd) met its co-primary endpoints of non-inferior objective response rate (ORR) and observed concentration before dosing (C trough) at steady state compared to intravenous (IV) Sarclisa administered at a weight-based dose in combination with Pd in patients with relapsed or refractory multiple myeloma (R/R MM). Key secondary endpoints, including very good partial response (VGPR), incidence rate of infusion reactions and C trough at cycle 2 were also achieved. The study is ongoing, and the full results will be presented at a forthcoming medical meeting."

P3 data • Multiple Myeloma

Trial in Progress: Phase 2 Study of Subcutaneous Isatuximab, Administered By an on-Body Delivery System, in Combination with Weekly Carfilzomib and Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma (SubQSA) (ASH 2024) - P1, P2 | "Intravenous (IV) Isa is currently approved to treat relapsed and/or refractory multiple myeloma (RRMM) in combination with pomalidomide and dexamethasone (Isa-Pd) or carfilzomib and dexamethasone (Isa-Kd)...In addition to dexamethasone, patients will receive premedication for IRs with montelukast (C1 only), acetaminophen, and diphenhydramine...ORR will be summarized with a two-sided 95% confidence interval by the Clopper-Pearson method. This study is not yet recruiting."

Clinical • Combination therapy • P2 data • Hematological Malignancies • Lymphoma • Multiple Myeloma • Oncology

Multicenter Phase 2 Study of Subcutaneous Isatuximab Plus Bortezomib, Lenalidomide and Dexamethasone in the Treatment of Newly Diagnosed Transplant Ineligible Multiple Myeloma (clinicaltrials.gov) - P=N/A | N=74 | Active, not recruiting | Sponsor: Poitiers University Hospital | Trial primary completion date: Jul 2024 ➔ Jul 2026

Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Safety, Pharmacokinetics, and Efficacy of Subcutaneous Isatuximab in Adults With Warm Autoimmune Hemolytic Anemia (wAIHA) (clinicaltrials.gov) - P2 | N=8 | Terminated | Sponsor: Sanofi | Phase classification: P1b/2 ➔ P2

Phase classification • Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immunology

SubQSA: A Study to Investigate Subcutaneous Isatuximab in Combination With Weekly Carfilzomib and Dexamethasone in Adult Participants With Relapsed and/or Refractory Multiple Myeloma (clinicaltrials.gov) - P2 | N=64 | Not yet recruiting | Sponsor: Sanofi | Initiation date: Jun 2024 ➔ Nov 2024

Combination therapy • Trial initiation date • Hematological Malignancies • Multiple Myeloma • Oncology

Successful Desensitization to Isatuximab in a Patient With Refractory Multiple Myeloma and Indolent Systemic Mastocytosis. Reply to: Anaphylactic Shock due to Isatuximab and Successful Desensitization. (PubMed, J Investig Allergol Clin Immunol) - No abstract available

Journal • Hematological Malignancies • Multiple Myeloma • Oncology

SC Versus IV Isatuximab in Combination With Pomalidomide and Dexamethasone in RRMM (clinicaltrials.gov) - P3 | N=534 | Active, not recruiting | Sponsor: Sanofi | Recruiting ➔ Active, not recruiting | Trial primary completion date: May 2024 ➔ Nov 2024

Combination therapy • Enrollment closed • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

A Study to Investigate Subcutaneous Isatuximab in Combination With Carfilzomib and Dexamethasone in Adult Participants With Relapsed and/or Refractory Multiple Myeloma (clinicaltrials.gov) - P2 | N=71 | Active, not recruiting | Sponsor: Sanofi | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Hematological Malignancies • Multiple Myeloma • Oncology

Final results: Phase 1b study of subcutaneous isatuximab administration by OBDS plus pomalidomide–dexamethasone in RRMM (BSH 2024) - P1, P3 | " This study SC versus IV Isa+Pd in RRMM pts with ≥2 prior treatment lines including lenalidomide and a proteasome inhibitor. Final results with SC Isa administration via OBDS at the 1400mg RP2D+Pd show an efficacy and safety profile consistent with IV administration, with no IRs, and excellent local tolerability. A non-inferiority phase 3 trial (NCT05405166) evaluating SC Isa via OBDS versus IV Isa is ongoing."

Clinical • P1 data • Infectious Disease • Multiple Myeloma • Novel Coronavirus Disease

Multicenter Phase 2 Study of Subcutaneous Isatuximab Plus Bortezomib, Lenalidomide and Dexamethasone in the Treatment of Newly Diagnosed Transplant Ineligible Multiple Myeloma (clinicaltrials.gov) - P=N/A | N=74 | Active, not recruiting | Sponsor: Poitiers University Hospital | Recruiting ➔ Active, not recruiting

Enrollment closed • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Multi-center, Open-label, Phase 1b Study in Patients With Relapsed/Refractory Multiple Myeloma (RRMM) (clinicaltrials.gov) - P1 | N=56 | Completed | Sponsor: Sanofi | Active, not recruiting ➔ Completed

Combination therapy • Trial completion • Hematological Malignancies • Multiple Myeloma • Oncology

SubQSA: A Study to Investigate Subcutaneous Isatuximab in Combination With Weekly Carfilzomib and Dexamethasone in Adult Participants With Relapsed and/or Refractory Multiple Myeloma (clinicaltrials.gov) - P2 | N=64 | Not yet recruiting | Sponsor: Sanofi

Combination therapy • New P2 trial • Hematological Malignancies • Multiple Myeloma • Oncology