Idefirix
Idefirix Uses, Dosage, Side Effects, Food Interaction and all others data.
Chronic kidney disease (CKD) is a progressive and irreversible disease that represents a significant burden for both the individual and healthcare system at large. Currently available treatments for end-stage renal disease are limited to dialysis and renal transplantation, with the former associated with significant costs and lower quality of life.
Patients who have developed human leukocyte antigen (HLA) sensitization from prior exposure to blood products, pregnancy, or any other circumstance which may have resulted in exposure to non-self HLA antigens, face additional barriers to transplantation. Highly sensitized individuals carry high levels of anti-HLA antibodies and are at significant risk for antibody-mediated rejection which occurs mainly through complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). High levels of anti-HLA antibodies also contribute to poor graft survival. As a result, highly sensitized individuals experience marked delays on transplant lists due to the challenges associated with procuring an HLA compatible donor graft.
Idefirix is a cysteine protease and eliminates Fc-dependent effector functions such as CDC and ADCC by cleaving the heavy chains of human immunoglobulin G (IgG) antibodies. As a result, the risk of antibody-mediated rejection is reduced allowing kidney transplantation in highly sensitized patients to proceed.
| Trade Name | Idefirix |
| Generic | Imlifidase |
| Imlifidase Other Names | HMED-IdeS, IdeS, IdeS recombinant, Imlifidase |
| Type | |
| Formula | C1575H2400N422O477S6 |
| Protein binding | There is currently no evidence to suggest that imlifidase binds to any other protein besides its primary target - immunoglobulin G (IgG). Studies have demonstrated that imlifidase is highly specific for IgG and does not bind to any other human immunoglobulins. |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Idefirix is a cysteine protease that specifically cleaves human IgG antibodies, facilitating kidney transplantation in HLA sensitized patients.
Idefirix is indicated for desensitization of highly sensitized adult kidney transplant patients with a positive crossmatch against an available deceased donor. The treatment is reserved for patients unlikely to receive a transplant under the available kidney allocation system including prioritization programs for highly sensitized patients.
Idefirix is also used to associated treatment for these conditions: Desensitization
How Idefirix works
Idefirix is a cysteine protease derived from Streptococcus pyogenes which degrades immunoglobulin G (IgG) in a multistep process. In the first step, imlifidase cleaves one of the two IgG heavy chains at the lower hinge leaving the other intact, resulting in a single cleaved IgG molecule. In the second step, the second heavy chain is cleaved yielding one homodimeric Fc fragment and one F(ab’)2 fragment.
This process removes the ability of the F(ab’)2 fragments to participate in Fc-mediated functions including antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Ultimately, by degrading the entire IgG pool, imlifidase reduces donor-specific antibodies (DSA) and allows transplantation to occur.
Toxicity
There is currently no data for imlifidase administered at supra-therapeutic doses; therefore, toxicity information is not readily available. In cases of overdose, the patient should be carefully monitored and symptomatic treatment should be initiated as needed. Although there is no antidote to imlifidase, administration of intravenous IgG may correct depleted IgG levels.
Food Interaction
No interactions found.Volume of Distribution
The volume of distribution of imlifidase is reported to be 0.2 L/kg in the elimination phase.
Elimination Route
Given that imlifidase is administered intravenously, it is fully absorbed and bioavailable; imlifidase exposure is dose-proportional and predictable. After a dose of 0.25 mg/kg, the mean Cmax of imlifidase was 5.8 (4.2-8.9) ug/mL. Tmax occurs once infusion is complete or soon after. Food is not expected to impact the effectiveness or absorption of imlifidase.
Half Life
The mean distribution half-life of imlifidase is reported to be 1.8 hours, while the mean elimination half-life is reported to be 89 hours.
Clearance
The mean clearance value of imlifidase is reported to be 1.8 mL/h/kg.
Innovators Monograph
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