NAV

Imlifidase

This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Summary

Imlifidase is a cysteine protease that specifically cleaves human IgG antibodies, facilitating kidney transplantation in HLA sensitized patients.

Brand Names
Idefirix
Generic Name
Imlifidase
DrugBank Accession Number
DB15258
Background

Chronic kidney disease (CKD) is a progressive and irreversible disease that represents a significant burden for both the individual and healthcare system at large.2 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.1,2

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.1,3 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).1 High levels of anti-HLA antibodies also contribute to poor graft survival.1 As a result, highly sensitized individuals experience marked delays on transplant lists due to the challenges associated with procuring an HLA compatible donor graft.1,3

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.6 As a result, the risk of antibody-mediated rejection is reduced allowing kidney transplantation in highly sensitized patients to proceed.1,6

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Recombinant Enzymes
Protein Chemical Formula
C1575H2400N422O477S6
Protein Average Weight
Not Available
Sequences
Not Available
Synonyms
  • HMED-IdeS
  • IdeS
  • IdeS recombinant
  • Imlifidase
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Pharmacology

Indication

Imlifidase is indicated for desensitization of highly sensitized adult kidney transplant patients with a positive crossmatch against an available deceased donor.6 The treatment is reserved for patients unlikely to receive a transplant under the available kidney allocation system including prioritization programs for highly sensitized patients.6

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Associated Therapies
Contraindications & Blackbox Warnings
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Pharmacodynamics

Imlifidase is highly specific to all four human IgG subclasses and does not cleave any other immunoglobulins (IgM, IgA, IgE, IgD).1,7 The inactivation of human IgG antibodies occurs rapidly and efficiently after administration of imlifidase, with the effect lasting for several weeks.5

Mechanism of action

Imlifidase is a cysteine protease derived from Streptococcus pyogenes which degrades immunoglobulin G (IgG) in a multistep process.4,6 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.4,5,6

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).6,7 Ultimately, by degrading the entire IgG pool, imlifidase reduces donor-specific antibodies (DSA) and allows transplantation to occur.1,6

TargetActionsOrganism
AIgG heavy chain
cleavage
Absorption

Given that imlifidase is administered intravenously, it is fully absorbed and bioavailable; imlifidase exposure is dose-proportional and predictable.1,6 After a dose of 0.25 mg/kg, the mean Cmax of imlifidase was 5.8 (4.2-8.9) ug/mL.6 Tmax occurs once infusion is complete or soon after.1 Food is not expected to impact the effectiveness or absorption of imlifidase.6

Volume of distribution

The volume of distribution of imlifidase is reported to be 0.2 L/kg in the elimination phase.1

Protein binding

There is currently no evidence to suggest that imlifidase binds to any other protein besides its primary target - immunoglobulin G (IgG).7 Studies have demonstrated that imlifidase is highly specific for IgG and does not bind to any other human immunoglobulins.7

Metabolism

There is currently no imlifidase metabolism data available; however, it is thought to be eliminated via proteolysis.7

Route of elimination

Not Available

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.1

Clearance

The mean clearance value of imlifidase is reported to be 1.8 mL/h/kg.1

Adverse Effects
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Toxicity

There is currently no data for imlifidase administered at supra-therapeutic doses; therefore, toxicity information is not readily available.6 In cases of overdose, the patient should be carefully monitored and symptomatic treatment should be initiated as needed.6 Although there is no antidote to imlifidase, administration of intravenous IgG may correct depleted IgG levels.6

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
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interactions in your software
AbciximabThe therapeutic efficacy of Abciximab can be decreased when used in combination with Imlifidase.
AdalimumabThe therapeutic efficacy of Adalimumab can be decreased when used in combination with Imlifidase.
AducanumabThe therapeutic efficacy of Aducanumab can be decreased when used in combination with Imlifidase.
AlemtuzumabThe therapeutic efficacy of Alemtuzumab can be decreased when used in combination with Imlifidase.
AlirocumabThe therapeutic efficacy of Alirocumab can be decreased when used in combination with Imlifidase.
Food Interactions
No interactions found.

Products

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International/Other Brands
Idefirix
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
IdefirixInjection11 mgIntravenousHansa Biopharma Ab2020-12-16Not applicableEU flag
IdefirixInjection, powder, for solution11 mgIntravenousHansa Biopharma Ab2020-12-16Not applicableEU flag

Categories

ATC Codes
L04AA41 — Imlifidase
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available
Affected organisms
Not Available

Chemical Identifiers

UNII
UVJ7NL8S2P
CAS number
1947415-68-0

References

General References
  1. Al-Salama ZT: Imlifidase: First Approval. Drugs. 2020 Nov;80(17):1859-1864. doi: 10.1007/s40265-020-01418-5. [Article]
  2. Fraser SD, Blakeman T: Chronic kidney disease: identification and management in primary care. Pragmat Obs Res. 2016 Aug 17;7:21-32. doi: 10.2147/POR.S97310. eCollection 2016. [Article]
  3. Rees L, Kim JJ: HLA sensitisation: can it be prevented? Pediatr Nephrol. 2015 Apr;30(4):577-87. doi: 10.1007/s00467-014-2868-6. Epub 2014 Jul 26. [Article]
  4. Lorant T, Bengtsson M, Eich T, Eriksson BM, Winstedt L, Jarnum S, Stenberg Y, Robertson AK, Mosen K, Bjorck L, Backman L, Larsson E, Wood K, Tufveson G, Kjellman C: Safety, immunogenicity, pharmacokinetics, and efficacy of degradation of anti-HLA antibodies by IdeS (imlifidase) in chronic kidney disease patients. Am J Transplant. 2018 Nov;18(11):2752-2762. doi: 10.1111/ajt.14733. Epub 2018 Apr 17. [Article]
  5. Winstedt L, Jarnum S, Nordahl EA, Olsson A, Runstrom A, Bockermann R, Karlsson C, Malmstrom J, Palmgren GS, Malmqvist U, Bjorck L, Kjellman C: Complete Removal of Extracellular IgG Antibodies in a Randomized Dose-Escalation Phase I Study with the Bacterial Enzyme IdeS--A Novel Therapeutic Opportunity. PLoS One. 2015 Jul 15;10(7):e0132011. doi: 10.1371/journal.pone.0132011. eCollection 2015. [Article]
  6. EMA Summary of Product Characteristics - Idefirix (imlifidase) powder for concentrate for solution for infusion [Link]
  7. EMA Assessment Report - Idefirix (imlifidase) [Link]
KEGG Drug
D11470
Wikipedia
Imlifidase

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4RecruitingTreatmentChronic Hepatitis B Infection1
4Unknown StatusTreatmentViral Hepatitis B1
3RecruitingOtherLong Term Efficacy and Safety1
3RecruitingTreatmentAnti-Glomerular Basement Membrane Antibody Disease / Anti-Glomerular Basement Membrane Disease / Good Pasture Syndrome1
3RecruitingTreatmentKidney Transplantation in Highly Sensitized Patients2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
InjectionIntravenous11 mg
Injection, powder, for solutionIntravenous10 MG/ml
Injection, powder, for solutionIntravenous11 mg
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not Available

Targets

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Details1. IgG heavy chain (Protein Group)
Kind
Protein group
Organism
Not Available
Pharmacological action
Yes
Actions
Cleavage
General Function
Immunoglobulin receptor binding
Specific Function
Not Available
Components:
NameUniProt ID
Ig gamma-1 chain C regionP01857
Ig gamma-2 chain C regionP01859
Ig gamma-4 chain C regionP01861
Immunoglobulin heavy constant gamma 3P01860
References
  1. Al-Salama ZT: Imlifidase: First Approval. Drugs. 2020 Nov;80(17):1859-1864. doi: 10.1007/s40265-020-01418-5. [Article]

Drug created at May 20, 2019 15:05 / Updated at February 21, 2021 18:55