ASH Highlights PDUFA Dates for Subcutaneous Istuximab in Myeloma, CAR T-Cell Therapy for AML/ALL/MDS
Sanofi announced that the FDA set a Prescription Drug User Fee Act (PDUFA) date of April 23, 2026, for subcutaneous isatuximab in relapsed/refractory multiple myeloma. The approval decision follows positive phase 3 IRAKLIA study results showing non-inferior efficacy and pharmacokinetics compared to intravenous administration, officials said.
The FDA’s April 23, 2026, Prescription Drug User Fee Act (PDUFA) date for subcutaneous isatuximab in relapsed/refractory multiple myeloma follows Sanofi’s announcement of positive phase 3 IRAKLIA study results, officials said. The IRAKLIA trial (NCT05405166) is the first global phase 3 study evaluating a subcutaneous cancer treatment administered via an on-body delivery system (OBDS), according to Sanofi. It enrolled 531 patients across 252 global sites with relapsed/refractory multiple myeloma, randomized equally to receive either subcutaneous Sarclisa plus pomalidomide and dexamethasone (Pd) or intravenous Sarclisa plus Pd in 28-day cycles.
The co-primary endpoints of the study were met, demonstrating non-inferior objective response rate (ORR) and trough concentration (Ctrough) at steady state for the subcutaneous formulation compared to intravenous administration, Sanofi officials confirmed.
The subcutaneous arm received a fixed 1,400 mg dose weekly for four weeks, then every two weeks, while the intravenous arm was dosed by weight on the same schedule, records show. Patients enrolled had received at least one prior line of therapy, including lenalidomide and a proteasome inhibitor, and treatment continued until disease progression, unacceptable adverse events, or discontinuation. Sanofi announced these results on January 9, 2025.
The subcutaneous formulation aims to enhance patient experience by providing a more convenient administration route than intravenous infusion, according to company statements. The OBDS delivers the drug over a short period, reducing clinic time and potentially improving patient comfort. A survey of 12 nurses with experience using the OBDS in related trials found that 75% had direct experience with the device, and all agreed it facilitated a positive patient treatment experience. The survey, conducted among nurses involved in the GMMG-HD8 trials (NCT05804032), reported that the OBDS reduced clinic time by 60% compared to manual subcutaneous injection using a syringe, improved patient comfort by 50%, and reduced patient anxiety by 50%, according to the survey results.
Supporting data from the IZALCO phase 2 study (NCT05704049) further reinforce the potential benefits of subcutaneous isatuximab. The open-label, sequential design study involved 42 patients receiving manual subcutaneous injections via syringe and butterfly set, and 24 patients administered the drug using an on-body injector in the periumbilical region. Patients received a flat 1,400 mg subcutaneous dose of isatuximab combined with carfilzomib and dexamethasone. Carfilzomib dosing started at 20 mg/m² on days 1 and 2, escalating to 56 mg/m² on days 8, 9, 15, and 16 of cycle one, with similar dosing in subsequent cycles. Dexamethasone was administered at 20 mg intravenously or orally on specified days. The median time to first response was 1.05 months (95% CI, 0.986–1.216), and the median time to best response was 3.81 months (95% CI, 2.825–4.632). Median progression-free survival (PFS) was not reached at the time of reporting, with a 95% confidence interval of 13.14 months to not reached, indicating immature data, according to the study published in Blood Cancer Journal.
The FDA granted approval for isatuximab-irfc (Sarclisa) in combination with bortezomib, lenalidomide, and dexamethasone (VRd) for newly diagnosed multiple myeloma patients ineligible for autologous stem cell transplant on September 20, 2024. This approval was based in part on the IMROZ trial (NCT03319667), which randomized 446 patients aged 80 or younger in a 3:2 ratio to receive isatuximab plus VRd or VRd alone. The IMROZ trial reported a median PFS not reached for the isatuximab arm compared to 54.3 months for the control arm, with a hazard ratio of 0.60, according to trial records.
Additional ongoing trials include a high-risk smoldering multiple myeloma study (NCT04270409) evaluating isatuximab combined with lenalidomide and dexamethasone, and the GMMG-HD8 trial (NCT05804032), which is assessing subcutaneous isatuximab in newly diagnosed multiple myeloma patients. These studies aim to further define the role of subcutaneous isatuximab in various treatment settings.
Sanofi’s development of the subcutaneous formulation through the IRAKLIA and IZALCO studies is part of a broader effort to improve access to care and patient convenience in multiple myeloma treatment, according to company officials. The OBDS represents a novel delivery mechanism intended to reduce infusion-related burdens and clinic time, with ongoing nurse feedback and patient experience data supporting its use.
The FDA’s setting of the PDUFA date for subcutaneous isatuximab signals regulatory progress toward expanding treatment options for relapsed/refractory multiple myeloma. The approval decision will follow a comprehensive review of the IRAKLIA phase 3 data and associated safety and efficacy results, officials said.
