Sanofi's Sarclisa Shows Non-Inferior Efficacy with Novel On-Body Injector in Phase 3 Multiple Myeloma Trial
核心洞察
The IRAKLIA phase 3 study demonstrated that Sarclisa administered subcutaneously via an on-body injector achieved non-inferior efficacy compared to intravenous infusion, with objective response rates of 71.1% versus 70.5% respectively.
Patients receiving subcutaneous Sarclisa experienced significantly fewer systemic infusion reactions (1.5% versus 25%) and reported higher satisfaction rates (70% versus 53.4%) compared to intravenous administration.
The innovative delivery system using Enable Injections (搜索)' enFuse device successfully delivered 99.9% of injections with no significant safety concerns, potentially transforming multiple myeloma treatment administration.
New clinical data presented at the American Society of Clinical Oncology (ASCO) Annual Meeting demonstrate that Sarclisa (isatuximab) administered subcutaneously via an innovative on-body injector achieves comparable efficacy to intravenous infusion while significantly improving the patient treatment experience in relapsed or refractory multiple myeloma.
The pivotal IRAKLIA phase 3 study, the first to incorporate an on-body injector in multiple myeloma treatment, established non-inferiority between subcutaneous and intravenous administration across key efficacy endpoints. With a median follow-up of 12 months, the objective response rate with Sarclisa subcutaneous-pomalidomide-dexamethasone was 71.1% compared to 70.5% with the intravenous regimen (risk ratio 1.008; 95% CI: 0.903-1.126; p=0.0006).
Significant Reduction in Infusion Reactions
The subcutaneous formulation delivered a notable safety advantage, with systemic infusion reactions occurring in only 1.5% of patients compared to 25% of those receiving intravenous treatment (risk ratio 0.061; 95% CI: 0.022-0.164; p<0.0001). Nearly all infusion reactions were grade 1 or 2 and resolved within one day, with no patients discontinuing treatment due to systemic reactions.
"Results from the IRAKLIA phase 3 study represent a potentially transformational advancement in the administration of multiple myeloma treatment," said Xavier Leleu, MD, PhD, Head of the Department of Hematology and Myeloma Clinic at the Hôpital La Mileterie and study investigator. "These data not only establish non-inferiority between Sarclisa administered both subcutaneously and intravenously across several key endpoints but reinforce the positive impact that this on-body injector could have on the patient treatment experience."
Enhanced Patient Experience and Satisfaction
Patient satisfaction scores demonstrated the positive impact of the novel delivery method, with 70% of subcutaneous-treated patients reporting satisfaction or high satisfaction compared to 53.4% in the intravenous arm (OR 2.036; 95% CI: 1.425-2.908; p=0.0001). The on-body injector successfully delivered 99.9% of injections with no significant safety concerns related to the device.
The studies utilized Enable Injections (搜索)' enFuse hands-free on-body injector, an automated device designed to subcutaneously administer high-volume medicines with the click of a button. The device features a 30-gauge, hidden, and retractable needle that is smaller than commonly used large-volume subcutaneous injection needles, potentially supporting patient comfort.
Supporting Phase 2 Data
The complementary IZALCO phase 2 study evaluated Sarclisa subcutaneous administration in combination with carfilzomib and dexamethasone, achieving an objective response rate of 79.7% (95% CI: 68.8-88.2). Patient preference strongly favored the on-body injector, with 74.5% preferring this method versus 17% preferring manual injection (p=0.0004).
Only 2.7% of patients experienced grade 2 or lower infusion reactions with manual injection, and no infusion reactions occurred with on-body injector administration. Approximately 1% of injections were associated with local injection site reactions.
Pharmacokinetic Advantages
The subcutaneous formulation demonstrated superior pharmacokinetic profiles, with observed mean concentration before dosing at steady state of 499 μg/mL compared to 341 μg/mL with intravenous administration (geometric mean ratio 1.532; 90% CI: 1.316-1.784). Similar advantages were observed at the 4-week timepoint, with concentrations of 421 μg/mL versus 302 μg/mL respectively.
Addressing Clinical Challenges
"Our subcutaneous clinical program is rooted in our mission to address patient needs and reduce treatment burden in multiple myeloma," said Alyssa Johnsen, MD, PhD, Global Therapeutic Area Head, Immunology and Oncology Development at Sanofi. "We believe the novel on-body injector represents a significant innovation that could improve and streamline the treatment process for both patients and providers."
The on-body injector addresses significant challenges associated with manual large-volume subcutaneous administration, including labor-intensive processes for nurses, risk of strain and needlestick injuries, and the need for larger needles that may compromise patient comfort and increase anxiety.
Expanding Clinical Program
Sanofi is evaluating subcutaneous Sarclisa administration via on-body injector across multiple treatment settings. The ISASOCUT phase 2 study is examining the combination with bortezomib, lenalidomide, and dexamethasone in newly diagnosed multiple myeloma patients not eligible for autologous stem-cell transplant. The German-speaking Myeloma Multicenter Group HD8 phase 3 study is evaluating subcutaneous Sarclisa-VRd induction in transplant-eligible newly diagnosed patients.
Data from these studies will collectively form the basis for global regulatory submissions across all currently approved treatment lines. The IRAKLIA abstract was selected for inclusion in the 2025 Best of ASCO program, and results will be presented at the European Hematology Association Congress.
The safety and efficacy of Sarclisa administered subcutaneously via on-body injector remain investigational and have not been approved by any regulatory authority. Sarclisa is currently approved in more than 50 countries across multiple treatment lines for multiple myeloma, including combinations with pomalidomide-dexamethasone, carfilzomib-dexamethasone, and bortezomib-lenalidomide-dexamethasone in various patient populations.