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| Primary information |
|---|
| ID | 15776 |
| Therapeutic ID | Th1626 |
| Protein Name | Imlifidase |
| Sequence | >Th1626_Imlifidase
MDSFSANQEIRYSEVTPYHVTSVWTKGVTPPANFTQGEDVFHAPYVANQGWYDITKTFNGKDDLLCGAATAGNMLHWWFDQNKDQIKRYLEEHPEKQKINFNGEQMFDVKEAIDTKNHQLDSKLFEYFKEKAFPYLSTKHLGVFPDHVIDMFINGYRLSLTNHGPTPVKEGSKDPRGGIFDAVFTRGDQSKLLTSRHDFKEKNLKEISDLIKKELTEGKALGLSHTYANVRINHVINLWGADFDSNGNLKAIYVTDSDSNASIGMKKYFVGVNSAGKVAISAKEIKEDNIGAQVLGLFTLSTGQDSWNQTN
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| Molecular Weight | NA |
| Chemical Formula | C1575H2400N422O477S6 |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| 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.[A225836] |
| Description | Chronic kidney disease (CKD) is a progressive and irreversible disease that represents a significant burden for both the individual and healthcare system at large.[A225916] 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.[A225836,A225916] 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.[A225836,A225921] 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).[A225836] High levels of anti-HLA antibodies also contribute to poor graft survival.[A225836] As a result, highly sensitized individuals experience marked delays on transplant lists due to the challenges associated with procuring an HLA compatible donor graft.[A225836,A225921] Imlifidase 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.[L28001] As a result, the risk of antibody-mediated rejection is reduced allowing kidney transplantation in highly sensitized patients to proceed.[A225836,L28001] |
| Indication/Disease | Imlifidase is indicated for desensitization of highly sensitized adult kidney transplant patients with a positive crossmatch against an available deceased donor.[L28001] The treatment is reserved for patients unlikely to receive a transplant under the available kidney allocation system including prioritization programs for highly sensitized patients.[L28001] |
| Pharmacodynamics | Imlifidase is highly specific to all four human IgG subclasses and does not cleave any other immunoglobulins (IgM, IgA, IgE, IgD).[A225836,L28041] The inactivation of human IgG antibodies occurs rapidly and efficiently after administration of imlifidase, with the effect lasting for several weeks.[A226045] |
| Mechanism of Action | Imlifidase is a cysteine protease derived from _Streptococcus pyogenes_ which degrades immunoglobulin G (IgG) in a multistep process.[A226040,L28001] 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.[A226040,A226045,L28001] 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).[L28001,L28041] Ultimately, by degrading the entire IgG pool, imlifidase reduces donor-specific antibodies (DSA) and allows transplantation to occur.[A225836,L28001] |
| Toxicity | There is currently no data for imlifidase administered at supra-therapeutic doses; therefore, toxicity information is not readily available.[L28001] In cases of overdose, the patient should be carefully monitored and symptomatic treatment should be initiated as needed.[L28001] Although there is no antidote to imlifidase, administration of intravenous IgG may correct depleted IgG levels.[L28001] |
| Metabolism | There is currently no imlifidase metabolism data available; however, it is thought to be eliminated via proteolysis.[L28041] |
| Absorption | Given that imlifidase is administered intravenously, it is fully absorbed and bioavailable; imlifidase exposure is dose-proportional and predictable.[A225836,L28001] After a dose of 0.25 mg/kg, the mean Cmax of imlifidase was 5.8 (4.2-8.9) ug/mL.[L28001] Tmax occurs once infusion is complete or soon after.[A225836] Food is not expected to impact the effectiveness or absorption of imlifidase.[L28001] |
| The volume of distribution of imlifidase is reported to be 0.2 L/kg in the elimination phase.[A225836] |
| Clearance | The mean clearance value of imlifidase is reported to be 1.8 mL/h/kg.[A225836] |
| Categories | Antineoplastic and Immunomodulating Agents |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | IgG heavy chain |
| Brand Name | Idefirix |
| Company | Hansa Biopharma Ab |
| Brand Description | Hansa Biopharma Ab |
| Prescribed For | Intravenous |
| Chemical Name | 11 mg |
| Formulation | NA |
| Physical Appearance | The most common side effects with Idefirix (which may affect more than 1 in 10 people) are infections, including pneumonia (infection of the lungs), urinary tract infection and sepsis (blood poisoning). Other common side effects (which may affect up to 1 in 10 people) are pain and reactions around the infusion site, increased blood levels of certain liver enzymes, muscle pain, headache and flushing. |
| Route of Administration | Idefirix is for hospital use only and can only be obtained with a prescription. Idefirix treatment should only be prescribed and supervised by a doctor experienced in the use of immunosuppressive medicines (medicines that reduce the activity of the immune system, the body’s natural defences) and in the management of sensitised kidney transplant patients. |
| Recommended Dosage | Highly sensitised patients have high levels of antibodies (proteins in the blood that fight infections and other foreign cells) against the donor’s tissue, including immunoglobulin G (IgG) antibodies. This makes their body more likely to reject the donor organ. The active substance in Idefirix, imlifidase, is an enzyme (a protein) that breaks down the IgG antibodies, thereby reducing the likelihood of the body rejecting the donor kidney. |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |