ELREXFIO

What it is

Elranatamab is an IgG2 kappa bispecific antibody derived from two monoclonal antibodies, an anti-B cell maturation antigen (BCMA) monoclonal antibody and an anti-Cluster of differentiation 3 (CD3) monoclonal antibody. ELREXFIO is for subcutaneous injection only. It is available as a 40 mg/mL solution for injection, supplied in single-dose vials containing either 44 mg in 1.1 mL or 76 mg in 1.9 mL. Elranatamab binds B-cell maturation antigen expressed on plasma cells, plasmablasts, and multiple myeloma cells and CD3 expressed on T cells. Simultaneous binding of BCMA and CD3 by elranatamab leads to T-cell activation and proliferation and the release of pro-inflammatory cytokines, resulting in the lysis of BCMA-expressing tumour and normal cells.

Approved indications

— Adult patients with relapsed or refractory multiple myeloma who have received at least 3 prior therapies, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody and have demonstrated disease progression on the last therapy.

Dosing overview

The recommended doses of ELREXFIO subcutaneous injection are step-up doses of 12 mg on Day 1 and 32 mg on Day 4 followed by a full treatment dose of 76 mg weekly, from Week 2 to Week 24. For patients who have received at least 24 weeks of treatment with ELREXFIO and have maintained a response, the dosing interval should transition to an every two-week schedule. For patients who have received at least 24 weeks of treatment at the every two-week schedule and maintained a response, the dose interval should transition to an every four-week schedule. Treatment with ELREXFIO should be continued until disease progression or unacceptable toxicity. Pre-treatment medicinal products should be administered prior to the first three doses of ELREXFIO, which includes step-up dose 1 (12 mg), step-up dose 2 (32 mg), and the first full treatment dose (76 mg). The following pre-treatment medicinal products should be administered approximately 1 hour prior: paracetamol 500 mg orally (or equivalent), dexamethasone 20 mg orally or intravenously (or equivalent), and diphenhydramine 25 mg orally (or equivalent).

Key safety warnings

Cytokine release syndrome (CRS) can occur in patients receiving ELREXFIO. Neurological toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), and serious and life threatening reactions, can occur in patients receiving ELREXFIO. CRS occurred in 57.9% of patients who received ELREXFIO at the recommended dosing schedule, with Grade 1 CRS in 43.7% of patients, Grade 2 CRS in 13.7% of patients and Grade 3 CRS in 0.5% of patients. Due to the risk of severe reactions, hospitalisation is recommended for 48 hours after administration of the first step-up dose, and for 24 hours after administration of the second step-up dose. ICANS occurred in 3.3% of patients following treatment with ELREXFIO at the recommended dosing schedule, with Grade 1 ICANS in 0.5%, Grade 2 in 1.6% and Grade 3 in 1.1% of patients. The majority of patients had ICANS after the first step-up dose (2.7%). Recurrent ICANS occurred in 1.1% of patients. ELREXFIO can cause severe, life-threatening, or fatal infections. New or reactivated viral infections occurred during and/or following therapy with ELREXFIO, including cytomegalovirus (CMV) infection/reactivation. Progressive multifocal leukoencephalopathy (PML), which can be fatal, has been reported during therapy with ELREXFIO. ELREXFIO can cause neutropenia and febrile neutropenia. Complete blood cell counts should be monitored at baseline and periodically during treatment.

Contraindications

Hypersensitivity to the active substance or to any of the excipients.

PBS listing

The 44 mg in 1.1 mL strength has a PBS ex-manufacturer price of A$3496.00 and the 76 mg in 1.9 mL strength has a PBS ex-manufacturer price of A$6038.00. Both strengths are listed with authority required restriction.

Regulatory history

ELREXFIO was first listed on the ARTG on 28 June 2024, with two registered vial presentations (44 mg/1.1 mL and 76 mg/1.9 mL). ELREXFIO has provisional approval in Australia. The decision to approve this indication was made on the basis of the overall response rate in a single arm study. Continued approval of this indication depends on verification and description of benefit in confirmatory trials. PBAC initially did not recommend ELREXFIO in July 2024, but subsequently recommended it in March 2025 for relapsed or refractory multiple myeloma in patients who have received at least three prior lines of therapy.