IDEFIRIX

What it is

Idefirix is an 11 mg powder for concentrate for solution for infusion containing imlifidase produced in Escherichia coli cells by recombinant DNA technology. Imlifidase is a cysteine protease derived from the immunoglobulin G (IgG)-degrading enzyme of Streptococcus pyogenes that cleaves the heavy chains of all human IgG subclasses and IgG-type of B-cell receptor (BCR) but no other immunoglobulins. This medicinal product is subject to additional monitoring in Australia, which will allow quick identification of new safety information.

Approved indications

— Desensitisation treatment of highly sensitised adult kidney transplant candidates prior to kidney transplantation from a donor against whom there is a positive cross-match. The use of Idefirix should be reserved for patients who are otherwise unlikely to receive a kidney transplant.

Dosing overview

The dose is based on patient body weight (kg) and the recommended dose is 0.25 mg/kg administered as a single dose preferably within 24 hours before transplantation. One dose is adequate for crossmatch conversion in the majority of patients but, if needed, a second dose can be administered within 24 hours after the first dose. Idefirix is for intravenous use only following reconstitution and dilution, and the entire, fully diluted infusion should be administered over a period of 15 minutes.

Key safety warnings

Infusion-related reactions have been reported with imlifidase administration in clinical studies; if any serious allergic or anaphylactic reaction occurs, imlifidase therapy should be discontinued immediately and appropriate therapy initiated. Mild or moderate infusion-related reactions occurring during imlifidase treatment can be managed by temporarily interrupting the infusion and/or by administration of medicinal products such as antihistamines, antipyretics and corticosteroids, and an interrupted infusion can be restarted when the symptoms have abated. The temporary reduction of IgG by imlifidase must be taken into consideration; since the most common infections in patients with hypogammaglobulinaemia are respiratory tract infections, all patients should receive prophylactic oral antibiotics covering respiratory tract pathogens for 4 weeks in addition to standard of care infection prophylaxis. Antibody-mediated rejection (AMR) may occur as a consequence of rebound of donor-specific antibodies (DSA); patients with very high levels of DSA before transplantation are more likely to experience early AMR that requires intervention, and most patients in the clinical studies had rebound of DSA that peaked between 7 and 21 days after imlifidase treatment, with AMR occurring in approximately 30% of the patients. The re-appearance of DSAs and increased risk of AMR in highly sensitised patients require physician's previous experience from managing sensitised patients, resources and preparedness to diagnose and treat acute AMRs according to standard clinical practice, and management of patients should include close monitoring of anti-HLA (human leukocyte antigen) antibodies and serum or plasma creatinine as well as readiness to perform biopsies when AMR is suspected.

Contraindications

Hypersensitivity to the active substance or to any of the excipients. Ongoing serious infection. Thrombotic thrombocytopenic purpura (TTP); patients with this blood disorder may be at risk of developing serum sickness.

Key safety warnings (Interactions)

Imlifidase is a cysteine protease that specifically cleaves IgG; as a consequence, IgG-based medicinal products may be inactivated if given in connection with imlifidase, and antibody-based medicinal products cleaved by imlifidase include basiliximab, rituximab, alemtuzumab, adalimumab, denosumab, belatacept, etanercept, rabbit anti-thymocyte globulin (rATG) and intravenous immunoglobulin (IVIg).

Regulatory history

Idefirix (imlifidase 11 mg powder for concentrate for solution for infusion) was first listed on the ARTG on 2023-07-10. Idefirix received provisional approval for the desensitisation treatment of highly sensitised adult kidney transplant candidates; this decision was made based on limited data, and the TGA requires the submission of more comprehensive evidence for full registration.