Sanofi’s Sarclisa Escena becomes first anticancer drug approved for on-body injector delivery

Sanofi has received US FDA approval for Sarclisa Escena (isatuximab-irfc), a subcutaneous formulation of its anti-CD38 antibody delivered via an automated on-body injector (OBI), marking the first anticancer therapy to receive approval through this delivery mechanism. The approval covers all existing indications held by the intravenous Sarclisa formulation across newly diagnosed and relapsed or refractory multiple myeloma, positioning Sanofi to compete more directly with Johnson & Johnson’s daratumumab (Darzalex Faspro), which already offers a subcutaneous option.

Sarclisa Escena is administered at a fixed dose of 1,400 mg subcutaneously via the CirCLIQ OBI, developed by Cincinnati-based Enable Injections using its enFuse platform. The device uses a retractable 30-gauge needle and is designed to deliver high-volume biologics with minimal manual effort. Unlike the weight-based intravenous dosing of the original Sarclisa formulation, the subcutaneous version uses a fixed dose and can also be administered by manual injection, making it the only anti-CD38 monoclonal antibody in multiple myeloma to offer both OBI and manual subcutaneous options.

The pivotal evidence supporting approval came from the IRAKLIA trial (NCT05405166), a randomized, open-label Phase III non-inferiority study in adults with relapsed or refractory multiple myeloma who had received at least one prior line of therapy. The trial evaluated Sarclisa Escena via OBI combined with pomalidomide and dexamethasone against weight-based intravenous Sarclisa in the same regimen. The primary efficacy measure was objective response rate (ORR): Sarclisa Escena achieved an ORR of 71.1% versus 70.5% for the intravenous formulation, meeting the non-inferiority threshold (relative risk 1.008; 95% confidence interval: 0.903–1.126).

Isatuximab targets CD38, a glycoprotein highly expressed on malignant plasma cells, and exerts cytotoxic effects through antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, and direct apoptosis induction. The subcutaneous formulation does not alter the molecule’s mechanism but changes the pharmacokinetic profile; the IRAKLIA trial also evaluated Sarclisa Escena plasma trough concentrations at steady state as a co-primary endpoint, demonstrating comparable drug exposure to the intravenous route.

The competitive relevance of the Sarclisa Escena approval is sharpened by the multiple myeloma field’s rapid evolution. Daratumumab, which targets the same CD38 antigen, already holds approved subcutaneous labeling across overlapping combination regimens — including the recently approved combination of teclistamab and daratumumab subcutaneous for second-line multiple myeloma — and remains the dominant anti-CD38 therapy by prescription volume. Beyond CD38-directed antibodies, the myeloma landscape is also being shaped by novel mechanisms: Bristol Myers Squibb’s mezigdomide demonstrated a 52% reduction in progression risk in a Phase III trial, adding to the competitive pressure Sarclisa Escena must navigate in the relapsed setting.

For Sanofi, the OBI-based approval represents a delivery platform milestone as much as a clinical one. The company reported that more than 70,000 patients worldwide have received isatuximab-based regimens, and the subcutaneous formulation is already approved in the EU and UK. The US Sarclisa Escena approval extends that access with a hands-free administration option that, the company said, may reduce physical burden on nursing staff compared with manual high-resistance syringe injections.

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