Sanofi’s subcutaneous Sarclisa Escena approved in the US as first anticancer treatment administered via on-body injector

FDA Approves Sanofi's SC Sarclisa Escena with On-Body Injector

The US FDA has approved Sanofi's subcutaneous (SC) Sarclisa (isatuximab-irfc) Escena, administered via the CirCLIQ® on-body injector (OBI), for multiple myeloma (MM) across all existing indications of its intravenous (IV) formulation. This marks the first anticancer treatment to be administered through an OBI. The approval is supported by the pivotal IRAKLIA phase 3 study, which demonstrated non-inferiority in efficacy, pharmacokinetics, and safety compared to IV infusion, alongside significantly shorter treatment times and fewer infusion-related reactions, aiming to enhance the patient experience and streamline administration for healthcare providers.

• Demonstrated Non-Inferior Efficacy and Improved Safety Profile: The pivotal IRAKLIA phase 3 study showed that Sarclisa Escena administered subcutaneously via an OBI achieved similar efficacy, pharmacokinetics, and overall safety compared to the IV formulation. Specifically, in relapsed or refractory MM patients, the objective response rate was 71.1% for SC-Pd versus 70.5% for IV-Pd, establishing non-inferiority. Notably, systemic administration reactions were significantly lower with SC-Pd (1.5%) compared to IV-Pd (25%).
• Enhanced Patient Experience and Provider Convenience: The approval introduces a patient-centric administration method, offering a significantly shorter treatment time and fewer infusion-related reactions compared to IV administration. The hands-free CirCLIQ OBI, developed by Enable Injections, uses a retractable 30g needle and is designed to reduce the physical burden on nurses, providing greater flexibility for patient monitoring and interaction, thereby improving the overall treatment experience for both patients and healthcare professionals.
• Broad Regulatory Scope and Innovative Delivery: Sarclisa Escena is approved in the US for all existing indications of the IV formulation in multiple myeloma, making it the first anticancer treatment to be administered through an on-body injector. It is also the first MM treatment available by both SC OBI and manual SC administration, offering unprecedented flexibility and convenience in how this anti-CD38 monoclonal antibody therapy is delivered to patients.

Overcoming Administration Challenges in Multiple Myeloma Treatment

Despite meaningful advances in multiple myeloma (MM) therapy — including the incorporation of proteasome inhibitors, immunomodulatory agents, and monoclonal antibodies — the disease remains incurable, accounting for approximately 2% of annual cancer-related deaths. The expanding armamentarium of drug combinations, while broadening treatment options, simultaneously introduces complexity in therapeutic decision-making and heightens the challenge of managing relapse. Critically, drug resistance and clonal evolution continue to undermine long-term disease control across all major drug classes.

• Universal refractoriness across drug classes: All currently available classes of anti-MM agents — including proteasome inhibitors, immunomodulators, and monoclonal antibodies — eventually become refractory, with relapses occurring even after deep responses. Upfront use of regimens such as daratumumab combined with proteasome inhibitors and immunomodulators has improved survival outcomes but creates unique challenges at relapse.

• Resistance to immunotherapy: Treatment resistance frequently develops with novel immunotherapies, and the underlying mechanisms remain poorly understood. Identified resistance mechanisms include T-cell exhaustion, target antigen mutation or loss, high disease burden, and impaired death receptor signaling — the latter representing an emerging mechanism of resistance specific to T-cell–mediated immunotherapies.

• Adverse effect burden limiting therapeutic potential: The efficacy of both traditional chemotherapy and contemporary anti-MM agents is constrained by their toxicity profiles, which restrict dosing and therapeutic optimization across patient populations.

• Heterogeneity and lack of personalized tools: The biologically heterogeneous nature of MM necessitates personalized testing tools to identify individual drug sensitivities, yet variability in drug responses across patient samples continues to complicate treatment selection.

• Incomplete mechanistic understanding of resistance: A deeper characterization of malfunctioning gene expression and dysregulated signaling pathways — including those involving noncoding RNAs — is required to develop strategies capable of durably overcoming drug resistance and improving long-term outcomes.

IRAKLIA Study Validates Sarclisa Escena's Efficacy and Safety

Recent clinical investigations in multiple myeloma span a broad range of therapeutic modalities — from CAR-T and bispecific antibodies to proteasome inhibitor combinations and monoclonal antibody regimens. The studies below represent a cross-section of late-phase and real-world evidence shaping current treatment paradigms.

Sarclisa Escena: Enhancing Convenience for Patients and HCPs

Multiple myeloma remains an incurable hematologic malignancy, and despite meaningful therapeutic advances, disease relapse is nearly inevitable — particularly in patients with high-risk cytogenetics, heavily pretreated disease, or refractory profiles. The evolving treatment landscape has intensified focus on specific populations and mechanistic gaps that continue to drive clinical development priorities.

• Relapsed/refractory multiple myeloma (RRMM) represents the central area of unmet need, with no consensus treatment standard for patients refractory to proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies; triple- and penta-class refractory patients face particularly limited options and poor prognosis.

• Post-BCMA-therapy relapse constitutes an emerging and critical unmet need — while BCMA-directed CAR-T therapies (ide-cel, cilta-cel) and bispecific antibodies (teclistamab, elranatamab) have demonstrated superiority over conventional options, the majority of patients relapse within a year, often with antigen-negative disease, necessitating salvage strategies targeting alternative antigens such as GPRC5D and FcRH5.

• High-risk multiple myeloma, including high-risk smoldering myeloma (HR-SMM) and newly diagnosed patients with adverse cytogenetics, represents a population with disproportionately poor outcomes requiring dedicated clinical trial development rather than extrapolation from standard-risk populations.

• Older and functionally impaired patients — including those over 80 years and those with poor ECOG performance status — are frequently excluded from or underrepresented in pivotal trials; geriatric assessment (GA)-based trial designs are needed to guide treatment selection in this population.

• Racial and socioeconomic disparities in access are well-documented: Black or African American patients are diagnosed at twice the rate of White patients yet are significantly less likely to receive CAR-T therapy (OR = 0.33; 95% CI, 0.17–0.62), with Other Pacific Islander patients showing the highest rate of CAR-T eligibility without documented discussion at 50%.

• Resistance mechanisms — including T-cell exhaustion, target antigen modulation or loss, and immunosuppressive bone marrow microenvironment remodeling — remain insufficiently addressed by single-agent immunotherapy, supporting the rationale for combination immunotherapeutic strategies and next-generation multispecific constructs.

• Meaningful clinical benefit thresholds remain a concern at the regulatory and payer level: only 4 of 17 approved MM drugs (23.5%) demonstrated meaningful clinical benefit per ESMO-MCBS scoring, underscoring the need for long-term outcome data to support reimbursement decisions.

• Geographically underserved and resource-constrained settings, particularly in the Middle East and parts of Asia — where MM incident cases accounted for 35.8% of the global total in 2021 — require management frameworks adapted to local drug accessibility, infrastructure, and expertise.

On-Body Injector Reshapes Multiple Myeloma Treatment Landscape

The recent FDA approval of Sanofi's subcutaneous Sarclisa, delivered via the innovative CirCLIQ® on-body injector, marks a pivotal moment in the treatment of multiple myeloma. This isn't just another formulation; it's the first anticancer therapy to leverage an OBI, fundamentally reshaping how patients might experience their treatment journey. For individuals living with multiple myeloma, who often face prolonged and frequent hospital visits for intravenous infusions, this shift promises a significant reduction in treatment burden. The pivotal IRAKLIA study confirmed that this SC delivery maintains non-inferior efficacy, pharmacokinetics, and safety compared to the IV formulation, ensuring that convenience does not come at the expense of therapeutic benefit. Studies have consistently shown isatuximab's efficacy in various settings, including relapsed/refractory multiple myeloma (RRMM) in combination with pomalidomide-dexamethasone or carfilzomib-dexamethasone, and even in newly diagnosed, transplant-ineligible patients with bortezomib-lenalidomide-dexamethasone. It has also demonstrated benefit in patients previously exposed to or refractory to daratumumab, highlighting its utility across different lines of therapy.

This strategic move by Sanofi offers several key advantages. The OBI's ability to significantly shorten administration times and reduce infusion-related reactions directly addresses critical patient needs and healthcare system efficiencies. This could enhance patient adherence, improve quality of life, and free up valuable clinic resources. However, the competitive landscape for multiple myeloma treatments is dynamic, with other anti-CD38 antibodies and a pipeline of novel agents, including bispecific antibodies and CAR T-cell therapies, continually emerging. While the OBI provides a strong differentiator, successful real-world implementation will hinge on effective patient and caregiver training, as well as seamless integration into existing healthcare workflows. Despite the reduction in infusion reactions, their potential occurrence still necessitates careful management. Ultimately, this approval underscores a growing trend towards patient-centric drug development, where innovation in delivery methods is as crucial as the therapeutic agent itself, potentially paving the way for similar advancements across oncology.