Subcutaneous Isatuximab Non-Inferior to IV in Relapsed/Refractory Myeloma
In patients with RRMM, subcutaneous isatuximab plus Pd resulted in a non-inferior objective response rate (ORR) and comparable pre-dose concentrations at steady state compared to IV isatuximab plus Pd.
Subcutaneous isatuximab-irfc plus pomalidomide and dexamethasone was non-inferior to its IV formulation in relapsed/refractory multiple myeloma.
Meeting its co-primary endpoints, the phase 3 IRAKLIA trial (NCT05405166) found that subcutaneous isatuximab-irfc (Sarclisa) plus pomalidomide (Pomalyst) and dexamethasone (Pd) achieved non-inferior objective response rate (ORR) and steady-state trough concentration (Ctrough) compared to IV isatuximab plus Pd in patients with relapsed/refractory multiple myeloma.1
Key secondary end points, including very good partial response (VGPR), incidence rate of infusion reactions and Ctrough at cycle 2 were also met. The study is ongoing, and the full results will be presented at an upcoming medical meeting.
“The consistent ORR and comparable efficacy and safety profile observed in the IRAKLIA study for subcutaneous [isatuximab] represent an exciting advancement, offering insight into a potential new administration option for patients,” Sikander Ailawadhi, MD, professor of medicine, Division of Hematology/Oncology at Mayo Clinic Florida and principal investigator of the study, stated in a news 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.”
IRAKLIA is evaluating the noninferiority of subcutaneous isatuximab given at a fixed dose via an an-body delivery system (OBDS) vs weight-2/3 based dosed IV isatuximab in combination with Pd in adult patients with relapsed/refractory multiple myeloma.
The study was conducted using Enable Injections’ enFuse® hands-free OBDS, which was designed to administer high-volume medicines subcutaneously through an automated drug delivery technology. The enFuse device uses a hidden and retractable needle that is thinner compared with commonly used subcutaneous injection needles.
The study enrolled 531 patients across 252 global sites, who were randomly assigned 1:1 to receive subcutaneous or IV isatuximab in combination with Pd for 28-day cycles until disease progression, unacceptable adverse effects, or patient withdrawal.
In the investigational arm, isatuximab was administered at a fixed, weekly dose for 4 weeks during the first cycle and every 2 weeks thereafter. In the IV arm, isatuximab was administered at a weight-based dose via IV infusion every week for 4 weeks during the first cycle and every 2 weeks thereafter.
To be eligible for enrollment patients needed to have received a diagnosis of multiple myeloma with prior exposure to at least 1 line of therapy, including lenalidomide (Revlimid) and a proteasome inhibitor.2
The co-primary end points are ORR, defined as the proportion of patients with stringent complete response, complete response, VGPR, and partial response according to the 2016 International Myeloma Working Group criteria assessed by independent review committee, and observed Ctrough at steady state, defined as observed plasma concentrations for isatuximab.
“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, added.1 “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 health care 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.”
Regulatory filings in the US and European Union are expected during the first half of 2025.
References
- 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 9, 2025. https://www.sanofi.com/assets/dotcom/pressreleases/2025/2025-01-09-06-00-00-3006798-en.pdf
- SC versus IV isatuximab in combination with pomalidomide and dexamethasone in RRMM (IRAKLIA). Clinicaltrials.gov. Updated November 14, 2024. Accessed January 9, 2025. https://clinicaltrials.gov/study/NCT05405166
