The FDA has extended the target action date to review a BLA seeking the approval of subcutaneous isatuximab for multiple myeloma.
The FDA has extended the review period for a biologics license application (BLA) seeking the approval of subcutaneous isatuximab-irfc (Sarclisa) delivered via an on-body injector (OBI) in combination with approved standard-of-care regimens for the treatment of patients with multiple myeloma.1 The revised target action date is July 23, 2026.
The BLA would cover all currently approved indications for the intravenous (IV) formulation of isatuximab. If approved, isatuximab would represent the first anticancer therapy approved by the FDA for delivery via OBI.
Data from the phase 3 IRAKLIA trial (NCT05405166) presented at the
Patients in the subcutaneous arm (n = 263) experienced an overall response rate (ORR) of 71.1% compared with 70.5% for patients treated in the IV arm (n = 268), meeting one of the study’s coprimary end points (relative risk [RR], 1.008; 95% CI, 0.903-1.126; P = .0006). The very good partial response (VGPR) or better rates were 46.4% and 45.9%, respectively (RR, 1.011; 95% CI, 0.841-1.125; P < .0001).
The study also met its other coprimary end point, with subcutaneous isatuximab demonstrating non-inferiority to the IV formulation in regard to Ctrough at steady state on day 1 of cycle 6 (geometric mean ratio, 1.532; 90% CI, 1.316-1.784).
The OBI is a sterile, single-use, user-filled, wearable injector. The OBI delivers a flat dose, with no adjustments needed for body weight. The needle also remains hidden from the patient before, during, and after administration. No hyaluronidase is used within the subcutaneous formulation of isatuximab in the OBI, and the flow rate is individualized based on subcutaneous interstitial pressure.
The phase 3, randomized, international, open-label, non-inferiority study enrolled patients at least 18 years of age with relapsed/refractory multiple myeloma who had received at least 1 prior line of therapy. Patients were randomly assigned 1:1 and stratified by myeloma isotype, body weight, and number of prior lines of therapy.
In cycle 1, patients received subcutaneous isatuximab at 1400 mg on days 1, 8, 15, and 22, in combination with Pd; or IV isatuximab at 10 mg/kg on the same schedule in combination with Pd. In cycle 2 and beyond, isatuximab was administered subcutaneously at 1400 mg or via IV at 10 mg/kg on days 1 and 15 of each cycle, in combination with Pd. Treatment in both arms continued until progressive disease, unacceptable toxicity, or patient withdrawal.
Along with the primary end points of ORR and Ctrough at cycle 6, day 1, secondary end points comprised VGPR or better rate; Ctrough at cycle 2, day 1; incidence of infusion-related reactions (IRRs); and patient satisfaction.
IRRs were reported in 1.5% of patients in the subcutaneous arm (n = 263) compared with 25.0% of patients in the IV arm (n = 264; RR, 0.061; 95% CI, 0.022-0.164).
Any-grade treatment-emergent adverse effects (TEAEs) occurred in 97.0% of patients in the subcutaneous arm vs 96.6% of patients in the IV arm. The respective rates of grade 3 or higher TEAEs were 81.7% and 76.1%. Drug-related TEAEs of grade 3 or higher were reported in 65.8% and 64.4% of patients, respectively. Serious TEAEs were experienced by 52.9% of patients in the subcutaneous arm vs 48.1% of patients in the IV arm; the respective rates of drug-related serious TEAEs were 27.0% and 29.5%. Grade 5 TEAEs were reported in 6.8% of patients in the subcutaneous arm compared with 7.2% of patients in the IV arm.
TEAEs leading to permanent, full treatment discontinuation occurred in 8.4% of patients in the subcutaneous arm vs 8.7% of patients in the IV arm. Notably, no TEAEs led to the permanent, partial discontinuation of isatuximab in either arm; these did lead to permanent, partial discontinuation of pomalidomide (3.4% vs 5.3%) and dexamethasone (4.9% vs 2.7%). OBI-related TEAEs of any grade occurred in 3.4% of patients in the experimental arm.
