NAV

Eculizumab

Identification

Summary

Eculizumab is a recombinant humanized monoclonal antibody used to reduce the risk of hemolysis in paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS).

Brand Names
Soliris
Generic Name
Eculizumab
DrugBank Accession Number
DB01257
Background

Eculizumab is a monoclonal antibody that targets complement protein C5.7,1 Binding to this protein prevents the activation of a complement terminal complex, which is used to treat a number of autoimmune conditions.7,1,2

Eculizumab was granted FDA approval on 16 March 2007.7 In Q1 2023, the EMA's Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion of two formulations of eculizumab indicated for the treatment of paroxysmal nocturnal hemoglobinuria.9,10

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Structure
Protein Chemical Formula
Not Available
Protein Average Weight
148000.0 Da
Sequences
Not Available
Synonyms
  • Eculizumab
External IDs
  • 5G1.1
  • H5G1-1
  • H5G1.1
  • H5G11

Pharmacology

Indication

Eculizumab is indicated in the US to treat paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis, atypical hemolytic uremic syndrome to inhibit complement-mediated thrombotic microangiopathy, and neuromyelitis optica spectrum disorder (NMOSD).6,2 It is also indicated in EU to treat PNH in both adult and pediatric patients.11

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Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

Eculizumab is a monoclonal antibody that prevents the activation of terminal complement in some autoimmune conditions.7,1,2 Eculizumab has a long duration of action.7 Patients taking this medication should be vaccinated against Neisseria meningiditis as serious meningococcal infections have occurred in the past.7,2

Mechanism of action

Eculizumab is a monoclonal antibody that targets complement protein C5, preventing cleavage to C5a and C5b, and the formation of the terminal complement complex C5b-9.7,1,2 Inhibition of this complex prevents complement mediated intravascular hemolysis in paroxysmal nocturnal hemoglobunuria, complement mediated microangiopathy in atypical hemolytic uremic syndrome, and immune mediated inflammation and damage of the central nervous system in neuromyelitis optica spectrum disorder.7,6,2

TargetActionsOrganism
AComplement C5
antibody
Humans
Absorption

Eculizumab is administered by intravenous infusion so the bioavailability is 100%.7 This drug reaches a Cmax of 194±76µg/mL and Ctrough of 97±60µg/mL.7 The AUC was calculated to be 24,467.6µg*h/mL.4

Volume of distribution

The volume of distribution of eculizumab is 5-8L.7

Protein binding

Though protein binding data is scarce, eculizumab is unlikely to be protein bound as it is a monoclonal antibody.

Metabolism

Eculizumab is a monoclonal antibody and is expected to be metabolized to small peptides and amino acids.4,5

Route of elimination

Monoclonal antibodies are not eliminated in the urine, and only a small amount is excreted in bile.5 Most monoclonal antibodies are catabolized in lysosomes to amino acids.5

Half-life

The half life of eculizumab is 270-375h7 or 272±82h.3

Clearance

Pharmacokinetic properties in healthy patients have not been determined.4 In patients with rhematoid arthritis, there is an average clearance of 0.26mL/kg/h.4

Adverse Effects
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Toxicity

Overdoses of eculizumab are unlikely as it is administered under specialist supervision.8 In case of overdose, contact local poison control.8

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
AbataceptThe risk or severity of adverse effects can be increased when Eculizumab is combined with Abatacept.
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Eculizumab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Eculizumab.
Adenovirus type 7 vaccine liveThe risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Eculizumab.
AducanumabThe risk or severity of adverse effects can be increased when Eculizumab is combined with Aducanumab.
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Eculizumab.
AlefaceptThe risk or severity of adverse effects can be increased when Alefacept is combined with Eculizumab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Eculizumab.
AlirocumabThe risk or severity of adverse effects can be increased when Eculizumab is combined with Alirocumab.
Allogeneic processed thymus tissueThe therapeutic efficacy of Allogeneic processed thymus tissue can be decreased when used in combination with Eculizumab.
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Food Interactions
No interactions found.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
BekemvInjection, solution, concentrate300 mgIntravenousAmgen Technology (Ireland) Uc2023-05-16Not applicableEU flag
EpysqliInjection, solution, concentrate10 mg/mlIntravenousSamsung Bioepis Nl B.V.2023-06-09Not applicableEU flag
SolirisSolution10 mg / mLIntravenousAlexion Pharma Gmbh2009-05-25Not applicableCanada flag
SolirisInjection, solution, concentrate300 mg/30mLIntravenousAlexion Pharmaceuticals Inc.2007-04-02Not applicableUS flag
SolirisInjection, solution, concentrate300 mgIntravenousAlexion Europe Sas2016-09-08Not applicableEU flag

Categories

ATC Codes
L04AA25 — Eculizumab
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
  • Humans and other mammals

Chemical Identifiers

UNII
A3ULP0F556
CAS number
219685-50-4

References

General References
  1. Thomas TC, Rollins SA, Rother RP, Giannoni MA, Hartman SL, Elliott EA, Nye SH, Matis LA, Squinto SP, Evans MJ: Inhibition of complement activity by humanized anti-C5 antibody and single-chain Fv. Mol Immunol. 1996 Dec;33(17-18):1389-401. [Article]
  2. Dmytrijuk A, Robie-Suh K, Cohen MH, Rieves D, Weiss K, Pazdur R: FDA report: eculizumab (Soliris) for the treatment of patients with paroxysmal nocturnal hemoglobinuria. Oncologist. 2008 Sep;13(9):993-1000. doi: 10.1634/theoncologist.2008-0086. Epub 2008 Sep 10. [Article]
  3. Rother RP, Rollins SA, Mojcik CF, Brodsky RA, Bell L: Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Nat Biotechnol. 2007 Nov;25(11):1256-64. [Article]
  4. Wijnsma KL, Ter Heine R, Moes DJAR, Langemeijer S, Schols SEM, Volokhina EB, van den Heuvel LP, Wetzels JFM, van de Kar NCAJ, Bruggemann RJ: Pharmacology, Pharmacokinetics and Pharmacodynamics of Eculizumab, and Possibilities for an Individualized Approach to Eculizumab. Clin Pharmacokinet. 2019 Jul;58(7):859-874. doi: 10.1007/s40262-019-00742-8. [Article]
  5. Ryman JT, Meibohm B: Pharmacokinetics of Monoclonal Antibodies. CPT Pharmacometrics Syst Pharmacol. 2017 Sep;6(9):576-588. doi: 10.1002/psp4.12224. Epub 2017 Jul 29. [Article]
  6. FDA: Eculizumab New Indication [Link]
  7. FDA Approved Drug Products: Eculizumab Intravenous Infusion [Link]
  8. Alexion Pharma: Soliris Product Monograph [Link]
  9. CHMP Summary of Positive Opinion: Bekemv (eculizumab) [Link]
  10. CHMP Summary of Positive Opinion: Epysqli (eculizumab) [Link]
  11. EMA Approved Drug Products: Epysqli (Eculizumab) solution for infusion [Link]
  12. FDA Approved Drug Products: SOLIRIS (eculizumab) injection, for intravenous use [Link]
PubChem Substance
46505429
RxNav
591781
ChEMBL
CHEMBL1201828
Therapeutic Targets Database
DAP000967
PharmGKB
PA164776637
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Eculizumab

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentAtypical Hemolytic Uremic Syndrome (aHUS)1
4CompletedTreatmentParoxysmal Hemoglobinuria1
4CompletedTreatmentParoxysmal Nocturnal Haemoglobinuria (PNH)1
4RecruitingTreatmentAtypical Hemolytic Uremic Syndrome (aHUS)1
3Active Not RecruitingTreatmentGeneralized Myasthenia Gravis / Myasthenia Gravis / Myasthenia Gravis, Juvenile Form1
3Active Not RecruitingTreatmentParoxysmal Nocturnal Haemoglobinuria (PNH)1
3CompletedEducational/Counseling/TrainingParoxysmal Hemoglobinuria1
3CompletedPreventionLeukemias1
3CompletedTreatmentAntibody Mediated Rejection / Cardiac Allograft Vasculopathy / Heart Graft Dysfunction / Hyperacute Rejection of Cardiac Transplant / Left Ventricular Dysfunction1
3CompletedTreatmentGuillain-Barré Syndrome (GBS)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Alexion Pharmaceuticals Inc.
  • Ben Venue Laboratories Inc.
Dosage Forms
FormRouteStrength
Injection, solution, concentrate300 mg/30ml
Injection, solution, concentrateIntravenous10 mg/ml
Injection, solution, concentrateIntravenous300 mg
Injection, solution, concentrateIntravenous300 mg/30mL
Injection, solution, concentrateIntravenous; Parenteral300 MG
SolutionIntravenous10 mg / mL
Solution, concentrateIntravenous300 mg
Injection, solution, concentrateParenteral300 mg/30ml
SolutionIntravenous300 mg
Prices
Unit descriptionCostUnit
Soliris 300 mg/30 ml vial210.0USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
CA2189015No2010-04-132015-04-30Canada flag

Properties

State
Liquid
Experimental Properties
Not Available

Targets

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Details1. Complement C5
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antibody
General Function
Receptor binding
Specific Function
Activation of C5 by a C5 convertase initiates the spontaneous assembly of the late complement components, C5-C9, into the membrane attack complex. C5b has a transient binding site for C6. The C5b-C...
Gene Name
C5
Uniprot ID
P01031
Uniprot Name
Complement C5
Molecular Weight
188303.705 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
  3. Singer AL, Locke JE, Stewart ZA, Lonze BE, Hamilton JP, Scudiere JR, Anders RA, Rother RP, Brodsky RA, Cameron AM: Successful liver transplantation for Budd-Chiari syndrome in a patient with paroxysmal nocturnal hemoglobinuria treated with the anti-complement antibody eculizumab. Liver Transpl. 2009 May;15(5):540-3. doi: 10.1002/lt.21714. [Article]
  4. Kelly R, Richards S, Hillmen P, Hill A: The pathophysiology of paroxysmal nocturnal hemoglobinuria and treatment with eculizumab. Ther Clin Risk Manag. 2009;5:911-21. Epub . [Article]
  5. Dmytrijuk A, Robie-Suh K, Cohen MH, Rieves D, Weiss K, Pazdur R: FDA report: eculizumab (Soliris) for the treatment of patients with paroxysmal nocturnal hemoglobinuria. Oncologist. 2008 Sep;13(9):993-1000. doi: 10.1634/theoncologist.2008-0086. Epub 2008 Sep 10. [Article]
  6. Rother RP, Rollins SA, Mojcik CF, Brodsky RA, Bell L: Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Nat Biotechnol. 2007 Nov;25(11):1256-64. [Article]
  7. Luzzatto L, Risitano AM, Notaro R: Paroxysmal nocturnal hemoglobinuria and eculizumab. Haematologica. 2010 Apr;95(4):523-6. doi: 10.3324/haematol.2009.017848. [Article]
  8. Hillmen P, Young NS, Schubert J, Brodsky RA, Socie G, Muus P, Roth A, Szer J, Elebute MO, Nakamura R, Browne P, Risitano AM, Hill A, Schrezenmeier H, Fu CL, Maciejewski J, Rollins SA, Mojcik CF, Rother RP, Luzzatto L: The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2006 Sep 21;355(12):1233-43. [Article]
  9. Hillmen P, Muus P, Duhrsen U, Risitano AM, Schubert J, Luzzatto L, Schrezenmeier H, Szer J, Brodsky RA, Hill A, Socie G, Bessler M, Rollins SA, Bell L, Rother RP, Young NS: Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria. Blood. 2007 Dec 1;110(12):4123-8. Epub 2007 Aug 16. [Article]
  10. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]

Drug created at May 16, 2007 16:57 / Updated at June 20, 2023 09:00