SARCLISA (isatuximab), a product of Sanofi, is a monoclonal antibody that binds to the CD38 receptor on multiple myeloma cells. It is basically manufactured and designed to initiate programmed tumor cell death (apoptosis) and immunomodulatory activity. 

At the 2025 EHA Congress, trial results confirmed that the SC on-body injector (OBI) form of isatuximab, used with pomalidomide and dexamethasone, was non-inferior to the intravenous (IV) isatuximab plus pomalidomide and dexamethasone regimen in terms of overall response rate (ORR). Isatuximab SC OBI plus pomalidomide and dexamethasone showed an ORR of 71.1% (n = 263), closely matching the 70.5% seen with isatuximab IV plus pomalidomide and dexamethasone (n = 268), with a relative risk (RR) of 1.008 (95% CI: 0.903–1.126; p = 0.0006), exceeding the noninferiority margin of 0.839.

Response depth was comparable across both groups. In the SC arm, 24.7% achieved a partial response, 28.5% a very good partial response (VGPR), and 17.9% a stringent complete or complete response (sCR/CR), versus 24.6%, 25.4%, and 20.5% in the IV arm. The rate of VGPR or better—another key secondary endpoint—was 46.4% for isatuximab SC OBI compared to 45.9% for isatuximab IV, with an RR of 1.011 (95% CI: 0.841–1.215; p < 0.0001), also meeting the noninferiority criteria. Pharmacokinetic (PK) data further supported noninferiority. Predose steady-state (Ctrough) levels on Day 1 of cycle 6 yielded a geometric mean ratio (GMR) of 1.532 (90% CI: 1.316–1.784), and on day 1 of cycle 2, the GMR was 1.302 (95% CI: 1.158–1.465), both well above the 0.8 noninferiority threshold.

The flat-dose formulation of the subcutaneous on-body injector (isatuximab SC OBI) maintained consistent overall response rates (ORR) across all body weight categories. Specifically, the relative risk was 0.928 (95% CI: 0.748–1.444) for patients ≤65 kg, 1.009 (95% CI: 0.850–1.197) for those between 65–85 kg, and 1.115 (95% CI: 0.915–1.372) for those >85 kg. isatuximab SC OBI also provided sufficient drug exposure across weight groups, as shown by Ctrough levels on cycle 2, Day 1—identified as the most reliable indicator of efficacy in exposure-response studies.

A key secondary endpoint assessed patient satisfaction at cycle 5, Day 15. In the intent-to-treat group, significantly more patients favored isatuximab SC OBI over the IV formulation—70.0% versus 53.4% (odds ratio: 2.036; 95% CI: 1.425–2.908; p = 0.0001), underscoring the positive impact of the SC delivery system on the treatment experience. Among patients in the isatuximab SC OBI arm who completed the satisfaction questionnaire (n = 190), 47.9% reported being satisfied and 48.9% were very satisfied. In comparison, among those receiving isatuximab IV (n = 202), 52.5% were satisfied and only 18.3% were very satisfied.

Grade ≥3 treatment-emergent adverse events occurred in 81.7% of patients in the SC OBDS arm and 76.1% of patients in the IV arm; with treatment discontinuation rates of 8.4% and 8.7%, respectively. Injection site reactions (ISRs) occurred in 4.2% (11/263) of patients in the SC arm and 19 (0.4%) of 5,145 SC injections; all were of Grade 1-2 severity. 99.9% of OBDS injections were completed without interruption.

KOL insights

"Coupled with a fast off rate and ability to detach from the BCMA target, the data provide us with a safe and efficacious product. IRAKLIA is the first multiple myeloma phase 3 study to incorporate the use of an innovative hands-free OBI, designed to maximize practice efficiency and patient convenience. These data support isatuximab SC OBI as a SOC administration for patients with multiple myeloma."– Expert Opinion

Conclusion

Monoclonal antibodies remain a cornerstone in the treatment of multiple myeloma, with agents targeting CD38 (e.g., DARZALEX, SARCLISA) and SLAMF7 (e.g., EMPLICITI) playing prominent roles. DARZALEX FASPRO, the first subcutaneous formulation, holds FDA approval across five treatment settings, including newly diagnosed and relapsed/refractory disease. 

With isatuximab now widely integrated into standard treatment protocols, its extended use underscores the importance of optimizing both administration efficiency and patient convenience. The IRAKLIA study was therefore launched to assess the utility of a novel on-body injector (OBI) for subcutaneous delivery. Findings from the trial suggest a revitalization of isatuximab’s market trajectory. While Sanofi’s later entry gave DARZALEX an early advantage, the introduction of the OBDS reflects the company’s commitment to innovation, overcoming prior manual administration hurdles and enhancing patient experience.

Despite SARCLISA's slower commercial uptake compared to DARZALEX, the adoption of the OBI system could shift dynamics in the anti-CD38 segment. The data from IRAKLIA reinforce the promise of this delivery method to streamline care and offer patients a more seamless treatment option, potentially strengthening SARCLISA’s future role in the evolving myeloma landscape.