Isatuximab Wins FDA Approval, Becoming Second Subcutaneous Anti-CD38 for Multiple Myeloma

The FDA has approved subcutaneous isatuximab-irfc (Sarclisa Escena; Sanofi), administered via an on-body injector, for the treatment of multiple myeloma. The approval gives clinicians another subcutaneous anti-CD38 monoclonal antibody option for this indication, joining subcutaneous daratumumab and hyaluronidase-fihj (Darzalex Faspro; Janssen Biotech) in a treatment landscape where anti-CD38-based regimens have become increasingly central to care.¹˒²

Isatuximab-irfc was approved in combination with standard-of-care regimens for patients with multiple myeloma across the existing indications of intravenous isatuximab.¹ The approval makes it the first anticancer treatment in the United States administered via an on-body injector and gives practices the option of administering isatuximab subcutaneously, in addition to intravenous isatuximab and manual subcutaneous administration.¹

The approval is significant not only because it adds a new formulation of isatuximab but also because it may alter how oncology pharmacists, infusion teams, and practices evaluate anti-CD38 administration, patient experience, and workflow in multiple myeloma. Daratumumab and hyaluronidase-fihj was first approved by the FDA in May 2020 as a subcutaneous CD38-directed antibody option for patients with multiple myeloma.² With the new approval, isatuximab adds another subcutaneous anti-CD38 pathway, differentiated by its on-body injector delivery system.¹

Anti-CD38 Therapy Continues to Reshape Frontline Multiple Myeloma Care

Matthew Lei, PharmD, BCOP, clinical pharmacy specialist in medical oncology/lymphoma, said the approval should be viewed within the broader evolution of anti-CD38 monoclonal antibody therapy in newly diagnosed multiple myeloma.

“The inclusion of anti-CD38 monoclonal antibodies into frontline regimens for patients with newly diagnosed multiple myeloma who are transplant eligible, ineligible, or deferred has led to a marked improvement in outcomes,” Lei said.

Lei noted modeled best-fit median progression-free survival estimates of 17.1 years in the PERSEUS trial (NCT04458051) and 8.3 years in the CEPHEUS trial (NCT03652064), emphasizing the impact of anti-CD38-based combinations in the frontline setting.³ In PERSEUS, modeling estimated a median progression-free survival of 17.1 years with daratumumab, bortezomib, lenalidomide, and dexamethasone followed by daratumumab-lenalidomide maintenance compared with 7.3 years with bortezomib, lenalidomide, and dexamethasone followed by lenalidomide maintenance.³ In CEPHEUS, the modeled median progression-free survival estimate was 8.3 years with daratumumab-based therapy compared with 4.4 years in the comparator arm.³

On-Body Injector May Improve Patient Experience and Workflow

Isatuximab is an anti-CD38 monoclonal antibody with mechanistic features that may distinguish it within the class. Lei explained that isatuximab can induce direct apoptosis of multiple myeloma cells, has less reliance on complement-dependent cytotoxicity, binds to a distinct epitope of CD38, inhibits CD38 enzymatic activity, and may produce downstream effects on the immune microenvironment and anti-myeloma drug sensitivity.⁴

From a patient-experience perspective, the on-body injector may offer another option for patients and practices. In the phase 3 IRAKLIA trial (NCT05405166), subcutaneous isatuximab administered by on-body injector demonstrated pharmacokinetic noninferiority to intravenous isatuximab, with comparable efficacy and safety and no unexpected safety signals.⁵ The trial data further supported the potential use of the on-body injector as a strategy to improve practice efficiency.⁵

In the phase 2 IZALCO trial (NCT05704049), which evaluated subcutaneous isatuximab administered by on-body injector or manual injection in combination with carfilzomib and dexamethasone in relapsed/refractory multiple myeloma, the overall response rate was 79.7% at a median follow-up of 10.1 months.⁵ Among patients evaluating delivery preference, 74.5% preferred the on-body injector, 17% preferred manual injection, and 8.5% reported no preference.⁶

“Subcutaneous isatuximab is hyaluronidase free and delivered as a 10 mL injection with a 30-gauge needle via a hands-free on-body injector,” Lei said. “It is battery-free and uses a small amount of pressure, approximately 7 psi, to individualize the flow rate, which is why patients reported less discomfort compared with manual subcutaneous injection on trial.”

Pharmacists Will Be Central to Implementation

For pharmacists, Lei said the approval introduces important considerations beyond drug selection alone. Practices will need to account for storage, preparation, dispensing, formulary status, treatment plan updates, and integration of both the medication and the device into existing workflows.

“Pharmacists will play an important role in facilitating access to isatuximab subcutaneous on-body injector,” Lei said. “There will need to be considerations for receipt and storage given the need to facilitate the medication-use process for not just the drug, but also the device.”

Implementation may vary by practice setting. Centers that already use intravenous isatuximab may need to evaluate the subcutaneous on-body injector as a line extension and update treatment pathways accordingly. Practices that do not currently use isatuximab may need to complete formulary onboarding and assess how to incorporate the product into existing medication-use processes.

Operationally, Lei said the on-body injector may reduce some hands-on administration burden because it replaces manual nurse-administered subcutaneous push with hands-free administration. He added that the device and drug combination, along with a needle-free preparation option, may also support resource savings for infusion pharmacies.

These workflow considerations may be especially important as oncology practices continue to balance patient volume, infusion chair capacity, staff time, and patient preference. For patients receiving ongoing anti-CD38 therapy, the administration route and comfort of delivery may influence the treatment experience, while pharmacy and nursing teams must ensure that new drug-device combinations can be incorporated safely and efficiently.

The approval adds a new practical option at a time when anti-CD38 monoclonal antibodies are increasingly embedded across multiple myeloma care. For oncology pharmacists, isatuximab-irfc may represent both a new administration option and an implementation consideration involving formulary review, product handling, device integration, treatment plan updates, and patient access.

As subcutaneous and device-enabled oncology therapies continue to enter practice, pharmacists will remain central to translating approvals into safe, efficient, and patient-centered care.

References

1. Sanofi. Sanofi’s subcutaneous Sarclisa Escena approved in the US as first anticancer treatment administered via on-body injector. News release. July 10, 2026. Accessed July 10, 2026. https://www.globenewswire.com/news-release/2026/07/10/3325483/0/en/press-release-sanofi-s-subcutaneous-sarclisa-escena-approved-in-the-us-as-first-anticancer-treatment-administered-via-on-body-injector.html

2. Janssen Biotech, Inc. FDA approves DARZALEX FASPRO, a new subcutaneous formulation of DARZALEX. News release. May 1, 2020. Accessed July 10, 2026. https://www.jhoponline.com/web-exclusives/fda-approves-darzalex-faspro-as-subcutaneous-formulation-for-all-patients-with-multiple-myeloma

3. Johnson & Johnson. New long-term progression-free survival data projections reinforce subcutaneous DARZALEX-based quadruplet therapy as a foundational standard of care for patients with newly diagnosed multiple myeloma. News release. May 2025. Accessed July 10, 2026. https://www.jnj.com/innovativemedicine/emea/newsroom/new-long-term-progression-free-survival-data-projections-reinforce-subcutaneous-darzalex-daratumumab-quadruplet-therapy-as-a-foundational-standard-of-care-for-patients-with-newly-diagnosed-multiple-myeloma

4. Zhu C, Song Z, Wang A, et al. Isatuximab Acts Through Fc-Dependent, Independent, and Direct Pathways to Kill Multiple Myeloma Cells. Front Immunol. 2020;11:1771. Published 2020 Aug 14. doi:10.3389/fimmu.2020.01771

5. Ailawadhi S, Špička I, Spencer A, et al. Isatuximab Subcutaneous by On-Body Injector Versus Isatuximab Intravenous Plus Pomalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma: Phase III IRAKLIA Study. J Clin Oncol. 2025;43(22):2527-2537. doi:10.1200/JCO-25-00744

6. Parmar G, Capra M, Seguro F, et al. Efficacy and safety of isatuximab subcutaneous plus carfilzomib and dexamethasone in patients with relapsed/refractory multiple myeloma: results of the Phase 2 study IZALCO. Blood Cancer J. 2025;16(1):16. Published 2025 Dec 27. doi:10.1038/s41408-025-01436-0