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| Primary information |
|---|
| ID | 15780 |
| 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 | Selective Immunosuppressants |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | IgG heavy chain |
| Brand Name | NA |
| Company | NA |
| Brand Description | NA |
| Prescribed For | NA |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | NA |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |