New Subcutaneous Formulation of Sarclisa Achieves Key Objectives in IRAKLIA Phase 3 Study for Multiple Myeloma
A subcutaneous (SC) formulation of Sarclisa, used alongside pomalidomide and dexamethasone (Pd) for treating relapsed or refractory multiple myeloma (R/R MM), has achieved the co-primary endpoints in the global IRAKLIA Phase 3 clinical trial.
The results demonstrated that the SC version was non-inferior in objective response rate (ORR) and steady-state pre-dosing concentration (C trough) compared to the intravenous (IV) formulation of Sarclisa combined with Pd. Key secondary goals, including very good partial response (VGPR), infusion reaction rates, and early-cycle C trough levels, were also met.
This study is the first of its kind to evaluate a subcutaneous cancer treatment delivered via an on-body delivery system (OBDS). The innovative device used in IRAKLIA, developed by Enable Injections, is designed to administer high-volume medications subcutaneously using automated technology. The OBDS features a hands-free mechanism with a thinner, retractable needle, aiming to enhance the patient experience compared to traditional SC injections.
The IRAKLIA trial was a randomized, open-label, pivotal Phase 3 study that compared the non-inferiority of fixed-dose Sarclisa administered SC through an OBDS to the weight-based IV version. Both formulations were evaluated in combination with Pd in adult patients with R/R MM. The trial enrolled 531 participants from 252 sites globally, dividing them evenly into two groups.
Participants receiving the SC version were treated weekly for the first four weeks of cycle one, followed by dosing every two weeks in subsequent cycles. In the IV group, Sarclisa was administered weekly during the initial cycle and every two weeks thereafter, with doses adjusted based on body weight. Treatment continued until disease progression, intolerable adverse effects, withdrawal, or other reasons.
Eligibility criteria included adults with multiple myeloma who had undergone at least one prior therapy, which included lenalidomide and a proteasome inhibitor.
Primary and Secondary Outcomes
The trial's co-primary endpoints were:
Objective Response Rate (ORR): Defined as the proportion of patients achieving stringent complete response, complete response, VGPR, or partial response, based on the 2016 International Myeloma Working Group (IMWG) criteria and reviewed by an Independent Review Committee (IRC).
Steady-State Pre-Dosing Concentration (C trough): Evaluated to ensure comparable pharmacokinetics between SC and IV formulations.
Additional secondary measures included VGPR rates, infusion-related reaction incidences, and early-cycle C trough levels.
Sarclisa (isatuximab) is a monoclonal antibody targeting CD38, a receptor expressed uniformly and abundantly on the surface of multiple myeloma cells. This treatment works through multiple mechanisms, including inducing programmed cell death (apoptosis) and modulating immune responses. By targeting CD38, Sarclisa leverages a highly specific approach to attacking cancer cells, making it a critical option for antibody-based therapies in multiple myeloma.
The new subcutaneous formulation of Sarclisa, paired with advanced delivery systems like OBDS, represents a significant advancement in patient-centered cancer care, offering an alternative to IV administration while maintaining efficacy and safety.
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