The Implications of Isatuximab-irfc’s FDA Approval for Multiple Myeloma

On July 9, 2026, the FDA approved Sarclisa Escena (isatuximab-irfc) for subcutaneous injection across three multiple myeloma treatment combinations, adding a delivery option to an anti-CD38 monoclonal antibody that had previously been available only as an intravenous infusion.¹

Three combinations were approved.¹ Isatuximab-irfc with pomalidomide and dexamethasone is approved for adult patients who have received at least 1 prior line of therapy that included lenalidomide and a proteasome inhibitor. Isatuximab-irfc with carfilzomib and dexamethasone is approved for adult patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy. Isatuximab-irfc with bortezomib, lenalidomide, and dexamethasone is approved for adult patients with newly diagnosed multiple myeloma who are not eligible for autologous stem cell transplant.

What Do the Clinical Data Show?

Efficacy of subcutaneous isatuximab-irfc with pomalidomide and dexamethasone was evaluated in IRAKLIA, an open-label, non-inferiority trial that randomized 531 patients evenly between subcutaneous administration, delivered through an on-body delivery system, and intravenous administration.¹ Overall response rate reached 71.1% in the subcutaneous group and 70.5% in the intravenous group, meeting the trial's non-inferiority threshold for that endpoint. A pharmacokinetic comparison also found that subcutaneous dosing produced higher steady-state trough drug concentrations than the intravenous formulation, with a geometric mean ratio of 1.53.

Two additional single-arm studies supported the other indications. In IZALCO, a phase 2 trial of the combination with carfilzomib and dexamethasone in 74 patients with relapsed or refractory disease, overall response rate was 79.7%.¹ In IsaSocut, an investigator-sponsored phase 2 study of 74 transplant-ineligible patients with newly diagnosed disease receiving isatuximab-irfc alongside bortezomib, lenalidomide, and dexamethasone, overall response rate reached 97.3%.

The prescribing information carries warnings for hypersensitivity and other administration-related reactions, neutropenia, infection, secondary primary malignancies, laboratory test interference, and embryo-fetal toxicity.¹ The recommended dose is 1400 mg, given subcutaneously either through the on-body delivery system or by syringe with a manual infusion set.

Why Does This Approval Matter Beyond the Clinic?

This approval is another data point in the industry's ongoing shift toward subcutaneous formulations for monoclonal antibodies originally built as intravenous infusions.¹ That shift carries real technical demands: high-concentration formulation work needed to fit a therapeutic dose into an injectable volume, device engineering for wearable delivery systems, and analytical characterization of how absorption and exposure differ from the intravenous route.

The change also reshapes site-of-care logistics.¹ Administration times measured in minutes rather than hours reduce chair time in infusion centers and open possibilities for at-home or community-based dosing. Warnings for hypersensitivity and other administration reactions still apply to the subcutaneous route, meaning monitoring protocols built around the intravenous formulation need to be reassessed. The FDA's willingness to rely on non-inferiority efficacy data paired with pharmacokinetic bridging data, rather than requiring new large-scale outcome trials, also illustrates how switching studies for reformulated biologics are increasingly being reviewed and accepted.

The application was supported by orphan drug designation and reviewed using the FDA's Assessment Aid, a voluntary submission format intended to streamline oncology review.¹

What Does the On-Body Injector Add to the Administration Picture?

The subcutaneous approval also introduced device-specific detail relevant to administration burden.² Sarclisa Escena's on-body injector (OBI), built on Enable Injections' enFuse platform, delivers the drug hands-free through a retractable 30-gauge needle designed for high-volume dosing. In the IRAKLIA trial, systemic administration reactions occurred in 1.5% of subcutaneous patients compared with 25% receiving intravenous dosing, while injection site reactions affected 0.4% of injections, nearly all low grade. As Sikander Ailawadhi, principal investigator of the IRAKLIA study, noted in a press release,² “The comparable efficacy observed across multiple studies and the patient-centric design of the OBI offers an opportunity to impact the patient experience while upholding Sarclisa's consistent efficacy.”

References

1. FDA approves isatuximab-irfc subcutaneous injection for multiple myeloma indications. U.S. Food and Drug Administration. Press Release. July 10, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-isatuximab-irfc-subcutaneous-injection-multiple-myeloma-indications
2. Sanofi’s subcutaneous Sarclisa Escena approved in the US as first anticancer treatment administered via on-body injector. Sanofi. Press Release. July 10, 2026. https://www.sanofi.com/en/media-room/press-releases/2026/2026-07-10-12-35-09-3325483