Subcutaneous Sarclisa Shows Non-Inferiority to IV Version for Multiple Myeloma in Phase III IRAKLIA Trial
Phase III IRAKLIA trial shows that subcutaneous Sarclisa delivered via an on-body delivery system is as effective and safe as intravenous administration in treating relapsed or refractory multiple myeloma.
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Results of the Phase III IRAKLIA trial (NCT05405166) found that a subcutaneous (SC) version of Sarclisa (isatuximab-irfc; Sanofi) administered with the combination of pomalidomide and dexamethasone (Pd) was noninferior to intravenous (IV) Sarclisa with Pd in objective response rate (ORR) and observed concentration before dosing (Ctrough) at steady state in the treatment of patients with relapsed or refractory multiple myeloma.1,2 The SC combination, delivered through an on-body delivery system (OBDS), may provide patients with a more convenient option for administration of treatment.
“The consistent overall response rate and comparable efficacy and safety profile observed in the IRAKLIA study for subcutaneous Sarclisa represent an exciting advancement, offering insight into a potential new administration option for patients,” principal trial investigator Sikander Ailawadhi, MD, professor of Medicine, Division of Hematology/Oncology at Mayo Clinic Florida, said in a press release. “The results from IRAKLIA, in patients with relapsed or refractory multiple myeloma, support the potential of an on-body delivery system to help ease the delivery of a new formulation without impacting patient outcomes.”1
Sarclisa is a targeted monoclonal antibody with prior approvals for patients with relapsed or refractory multiple myeloma, which is the second most common type of blood cancer.3,4
In September 2024, the FDA approved a supplemental Biologics License Application for Sarclisa combined with bortezomib, lenalidomide, and dexamethasone (VRd) to treat transplant-ineligible patients with newly diagnosed multiple myeloma.5 The regulatory action made Sarclisa the first anti-CD38 therapy indicated in combination with VRd for newly diagnosed patients who are ineligible for a transplant.
Trial Design
IRAKLIA is an ongoing, investigational, randomized, open-label trial. Investigators sought to establish noninferiority of SC Sarclisa administered at a fixed dose via Enable Injections’ enFuse hands-free OBDS compared to weight-based dosed IV Sarclisa plus Pd in adults with relapsed/refractory multiple myeloma. The enFuse OBDS was developed to deliver high-volume medications via SC administration through automated drug delivery technology. The enFuse system has a retractable needle that is thinner than current SC injection needles.
A total of 531 patients were enrolled at 252 global sites and randomly assigned in a 1:1 ratio to receive SC or IV Sarclisa plus Pd in 28-day cycles until disease progression, unacceptable adverse effects, or patient withdrawal.
In the SC cohort, Sarclisa was given at a fixed weekly dose for four weeks in the first cycle and every two weeks afterwards. In the IV cohort, Sarclisa was infused at a weight-based dose on a weekly basis for four weeks for the first cycle and every two weeks afterwards.
The trial’s co-primary endpoints are ORR, which was defined as proportion of patients with stringent complete response (CR); CR; very good partial response (VGPR); partial response as per 2016 International Myeloma Working Group criteria assessed by independent review committee; and observed Ctrough at steady state, which was defined as observed plasma concentrations for Sarclisa.
In addition to meeting the co-primary endpoints, the trial also achieved the key secondary endpoints of VGPR, incidence of infusion reactions, and Ctrough at cycle two. Full results from the trial will be presented at an upcoming medical meeting, according to Sanofi.
“We are fueled by our focus on innovation and finding best-in-class solutions to help ease the burden of disease for patients,” Houman Ashrafian, MD, PhD, executive vice president, head of Research and Development at Sanofi. “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. We look forward to sharing full results and working to bring this new advancement to the multiple myeloma community.”1
References
1. New Sarclisa subcutaneous formulation met co-primary endpoints in the IRAKLIA phase 3 study in multiple myeloma. News release. Sanofi. January 9, 2025. Accessed January 10, 2025. https://www.sanofi.com/en/media-room/press-releases/2025/2025-01-09-06-00-00-3006798
2. SC versus IV isatuximab in combination with pomalidomide and dexamethasone in RRMM (IRAKLIA). Clinicaltrials.gov. Updated November 14, 2024. Accessed January 10, 2025. https://clinicaltrials.gov/study/NCT05405166
3. FDA approves Sarclisa (isatuximab-irfc) for patients with relapsed multiple myeloma. News release. Sanofi-aventis U.S. LLC. March 2, 2020. Accessed January 10, 2025. https://www.sanofi.com/en/media-room/press-releases/2020/2020-03-02-19-51-16
4. Understanding SARCLISA. International Myeloma Foundation. Published June 2020. Accessed January 10, 2025. https://imf-d8-prod.s3.us-west-1.wasabisys.com/2020-06/U-Sarclisa.pdf
5. SARCLISA® Approved in the US as the First Anti-CD38 Therapy in Combination with Standard-of-Care Treatment for Adult Patients with Newly Diagnosed Multiple Myeloma not Eligible for Transplant. Sanofi. September 20, 2024. Accessed January 10, 2025. https://www.news.sanofi.us/2024-09-20-SARCLISA-R-approved-in-the-US-as-the-first-anti-CD38-therapy-in-combination-with-standard-of-care-treatment-for-adult-patients-with-newly-diagnosed-multiple-myeloma-not-eligible-for-transplant
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