Formulation Results from the IRAKLIA Phase 3 Study Demonstrate Promise for Subcutaneous Sarclisa in Multiple Myeloma
The Formulation IRAKLIA Phase 3 study has presented encouraging results for the investigational subcutaneous (SC) formulation of Sarclisa, administered through an on-body delivery system (OBDS), in combination with pomalidomide and dexamethasone (Pd) for patients with relapsed or refractory multiple myeloma (R/R MM). The study successfully met its co-primary endpoints, showing that the subcutaneous formulation of Sarclisa is non-inferior to the intravenous (IV) version of the medication in terms of both objective response rate (ORR) and observed concentration before dosing (C trough) at steady state.
The study was designed to compare the efficacy and pharmacokinetics of the fixed-dose, subcutaneous formulation of Sarclisa delivered via an OBDS to the standard weight-based intravenous dose. In addition to the co-primary endpoints, key secondary objectives, such as the rate of very good partial response (VGPR), incidence of infusion reactions, and C trough at cycle 2, were also successfully achieved. These promising results provide strong evidence for the potential of subcutaneous Sarclisa as a new and improved treatment option for patients with R/R MM, marking a significant step forward in the development of multiple myeloma therapies.
Study Design and Methodology
The Formulation IRAKLIA study is an ongoing, randomized, open-label trial that includes patients with relapsed or refractory multiple myeloma, a condition where the disease has either returned or is resistant to treatment. Patients were randomly assigned to receive either subcutaneous Sarclisa in combination with pomalidomide and dexamethasone or the standard intravenous formulation of Sarclisa in combination with the same medications.
The subcutaneous formulation of Sarclisa, delivered through the enFuse® hands-free OBDS, has been developed to improve the patient experience by offering a potentially more convenient and less time-consuming alternative to intravenous administration. This device is designed to administer high-volume medications subcutaneously using an automated drug delivery system, which offers the advantage of minimizing the need for healthcare professionals’ direct involvement. The enFuse device employs a retractable and thinner needle compared to those typically used for standard SC injections, potentially reducing the discomfort associated with injection.
Formulation The primary endpoints of the study aimed to demonstrate non-inferiority in both the objective response rate (ORR) and the observed concentration before dosing (C trough) at steady state. Both metrics are critical in assessing the clinical efficacy and pharmacokinetic behavior of the treatment, and the subcutaneous Sarclisa formulation met these objectives. Additionally, the achievement of key secondary endpoints such as VGPR and low rates of infusion reactions further solidified the positive outcome of the trial.
Clinical Impact and Significance
The results of the IRAKLIA study offer a promising outlook for the treatment of relapsed or refractory multiple myeloma, a challenging and often difficult-to-treat cancer. Multiple myeloma remains a significant burden on patients and healthcare systems, and the availability of more convenient and effective treatment options is a priority for the medical community.
Dr. Sikander Ailawadhi, Professor of Medicine in the Division of Hematology/Oncology at Mayo Clinic Florida and principal investigator of the IRAKLIA study, emphasized the importance of these findings in advancing the treatment landscape for multiple myeloma. “The consistent overall response rate and comparable efficacy and safety profile observed in the IRAKLIA study for subcutaneous Sarclisa represent an exciting advancement,” Dr. Ailawadhi stated. “These results offer insight into a potential new administration option for patients, and the data suggest that the on-body delivery system could ease the delivery of this new formulation without impacting patient outcomes.”
The ability to administer Sarclisa subcutaneously could significantly improve the patient experience by reducing the time spent in healthcare facilities for intravenous infusions, an important consideration given the chronic nature of multiple myeloma and the frequent treatments required. Additionally, the on-body delivery system, with its less intrusive and more patient-friendly design, may help reduce the physical discomfort typically associated with intravenous treatments.
Innovative Technology Behind the Delivery System
The enFuse® hands-free OBDS, developed by Enable Injections, represents a novel approach to delivering high-volume medications. The device was designed to support the subcutaneous administration of biologics, offering an automated and patient-friendly method for self-administration. Unlike traditional needle-and-syringe methods, the enFuse system uses an automated drug delivery technology to administer the medication with minimal direct intervention, providing patients with greater autonomy and convenience.
The retractable and thinner needle employed in the enFuse system is a key feature that differentiates it from other subcutaneous injection systems. Its design aims to reduce pain and discomfort, making it a more tolerable option for patients, particularly those who require frequent treatments. By minimizing the need for multiple healthcare visits and streamlining the administration process, this delivery system could help improve patient adherence to treatment regimens.
Dr. Houman Ashrafian, Executive Vice President and Head of Research and Development at Sanofi, highlighted the importance of innovation in patient care. “We are fueled by our focus on innovation and finding best-in-class solutions to help ease the burden of disease for patients,” Dr. Ashrafian said. “The IRAKLIA study results are a prime example of what’s driving our scientific engine. Being able to possibly bring a novel option that helps reduce time in a healthcare facility is driven by our patient- and provider-centric mindset.”
Ongoing and Future Studies
The IRAKLIA study is just one part of a larger body of research into the subcutaneous formulation of Sarclisa. Additional studies are ongoing to evaluate the safety and efficacy of Sarclisa SC in various combinations and across different lines of therapy for multiple myeloma. These studies aim to broaden the potential applications of Sarclisa SC and further establish its role in the treatment of R/R MM.
It is important to note that the safety and efficacy of Sarclisa SC, along with the enFuse device, have not yet been evaluated by regulatory authorities outside of their currently approved indications. Regulatory submissions in the United States and the European Union are planned for the first half of 2025. These submissions will play a crucial role in determining the broader availability of Sarclisa SC for multiple myeloma patients and its potential to become a standard treatment option.
