Identification

Name
Eculizumab
Accession Number
DB01257
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Description

Soliris is a formulation of eculizumab which is a recombinant humanized monoclonal IgG2/4;κ antibody produced by murine myeloma cell culture and purified by standard bioprocess technology. Eculizumab contains human constant regions from human IgG2 sequences and human IgG4 sequences and murine complementarity-determining regions grafted onto the human framework light- and heavy-chain variable regions. Eculizumab is composed of two 448 amino acid heavy chains and two 214 amino acid light chains and has a molecular weight of approximately 148 kDa.

Protein structure
Db01257
Protein chemical formula
Not Available
Protein average weight
148000.0 Da
Sequences
Not Available
Synonyms
  • 5G1.1
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
SolirisSolution10 mgIntravenousAlexion Pharma Emea Ghbh2009-05-25Not applicableCanada
SolirisInjection, solution, concentrate300 mgIntravenousAlexion Europe Sas2007-06-20Not applicableEu
SolirisInjection, solution, concentrate300 mg/30mLIntravenousAlexion Pharmaceuticals2007-04-02Not applicableUs
Categories
UNII
A3ULP0F556
CAS number
219685-50-4

Pharmacology

Indication

For the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis.

Structured Indications
Pharmacodynamics

Eculizumab is a monoclonal antibody directed against the complement protein C5. This antibody blocks the cleavage of C5 and halts the process of complement-mediated cell destruction. Eculizumab is a product of Alexion Pharmaceuticals and has been shown to be effective in treating paroxysmal nocturnal hemoglobinuria. Eculizumab was approved by the FDA in March, 2007.

Mechanism of action

A genetic mutation in PNH patients leads to the generation of populations of abnormal RBCs (known as PNH cells) that are deficient in terminal complement inhibitors (CD-59), rendering PNH RBCs sensitive to persistent terminal complement-mediated destruction. The destruction and loss of these PNH cells (intravascular hemolysis) results in low RBC counts (anemia) and also fatigue, difficulty in functioning, pain, dark urine, shortness of breath, and blood clots. Eculizumab, the active ingredient in Soliris, is a monoclonal antibody that binds to the complement protein C5 specifically and with high affinity, thereby inhibiting its cleavage to C5a and C5b and subsequent generation of the terminal complement complex C5b-9. Soliris inhibits terminal complement mediated intravascular hemolysis in PNH patients and therefore the destruction of PNH erythrocytes that lack complement protection with CD-59.

TargetActionsOrganism
AComplement C5
antibody
Human
Absorption
Not Available
Volume of distribution
  • 7.7 L
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

272 ± 82 hrs (mean ± SD)

Clearance
  • 22 mL/hr [typical PNH patient weighing 70 kg]
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Eculizumab.Investigational
BelimumabThe risk or severity of adverse effects can be increased when Eculizumab is combined with Belimumab.Approved
Clostridium tetani toxoid antigen (formaldehyde inactivated)The therapeutic efficacy of Clostridium tetani toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Eculizumab.Approved
Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated)The therapeutic efficacy of Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Eculizumab.Approved
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Eculizumab.Approved
FingolimodEculizumab may increase the immunosuppressive activities of Fingolimod.Approved, Investigational
G17DTThe therapeutic efficacy of G17DT can be decreased when used in combination with Eculizumab.Investigational
GI-5005The therapeutic efficacy of GI-5005 can be decreased when used in combination with Eculizumab.Investigational
Hepatitis A VaccineThe therapeutic efficacy of Hepatitis A Vaccine can be decreased when used in combination with Eculizumab.Approved
Hepatitis B Vaccine (Recombinant)The therapeutic efficacy of Hepatitis B Vaccine (Recombinant) can be decreased when used in combination with Eculizumab.Approved, Withdrawn
INGN 201The therapeutic efficacy of INGN 201 can be decreased when used in combination with Eculizumab.Investigational
INGN 225The therapeutic efficacy of INGN 225 can be decreased when used in combination with Eculizumab.Investigational
LeflunomideThe risk or severity of adverse effects can be increased when Eculizumab is combined with Leflunomide.Approved, Investigational
NatalizumabThe risk or severity of adverse effects can be increased when Eculizumab is combined with Natalizumab.Approved, Investigational
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Eculizumab.Approved, Investigational
Rabies virus inactivated antigen, AThe therapeutic efficacy of Rabies virus inactivated antigen, A can be decreased when used in combination with Eculizumab.Approved
RindopepimutThe therapeutic efficacy of Rindopepimut can be decreased when used in combination with Eculizumab.Investigational
RoflumilastRoflumilast may increase the immunosuppressive activities of Eculizumab.Approved
Rotavirus VaccineThe therapeutic efficacy of Rotavirus Vaccine can be decreased when used in combination with Eculizumab.Approved
Rubella virus vaccineThe therapeutic efficacy of Rubella virus vaccine can be decreased when used in combination with Eculizumab.Approved
Salmonella typhi ty21a live antigenThe therapeutic efficacy of Salmonella typhi ty21a live antigen can be decreased when used in combination with Eculizumab.Approved
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Eculizumab.Approved
SRP 299The therapeutic efficacy of SRP 299 can be decreased when used in combination with Eculizumab.Investigational
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Eculizumab.Approved, Investigational
TecemotideThe therapeutic efficacy of Tecemotide can be decreased when used in combination with Eculizumab.Investigational
TG4010The therapeutic efficacy of TG4010 can be decreased when used in combination with Eculizumab.Investigational
TofacitinibEculizumab may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
TrastuzumabTrastuzumab may increase the neutropenic activities of Eculizumab.Approved, Investigational
Yellow fever vaccineThe therapeutic efficacy of Yellow fever vaccine can be decreased when used in combination with Eculizumab.Approved
Zoster vaccineThe therapeutic efficacy of Zoster vaccine can be decreased when used in combination with Eculizumab.Approved
Food Interactions
Not Available

References

General References
  1. 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. [PubMed:16990386]
  2. 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. [PubMed:9171898]
  3. 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. [PubMed:18784156]
  4. 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. [PubMed:17989688]
External Links
PubChem Substance
46505429
ChEMBL
CHEMBL1201828
Therapeutic Targets Database
DAP000967
PharmGKB
PA164776637
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Eculizumab
ATC Codes
L04AA25 — Eculizumab
AHFS Codes
  • 92:32.00 — Complement Inhibitors

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Unknown StatusTreatmentDense Deposit Disease / Membranoproliferative Glomerulonephritis1
1Unknown StatusTreatmentKidney; Complications, Allograft1
1, 2CompletedTreatmentNeuromyelitis Optica1
1, 2TerminatedTreatmentTransplant, Kidney1
1, 2Unknown StatusTreatmentChronic Hemolysis1
1, 2WithdrawnTreatmentSubclinical Acute Antibody-mediated Rejection in Kidney Transplantation1
2Active Not RecruitingPreventionAntiphospholipid Antibody Syndrome / End Stage Renal Disease (ESRD)1
2Active Not RecruitingPreventionComplement Activity / Delayed Graft Function / Transplantation, Kidney1
2Active Not RecruitingTreatmentMembranoproliferative Glomerulonephritis1
2CompletedPreventionAsthma, Allergic1
2CompletedTreatmentAge-Related Macular Degeneration (ARMD)1
2CompletedTreatmentAlloimmune Platelet Refractoriness / Thrombocytopenias1
2CompletedTreatmentAtypical Hemolytic Uremic Syndrome (aHUS)5
2CompletedTreatmentAtypical Hemolytic-Uremic Syndrome2
2CompletedTreatmentCold type haemolytic anaemia1
2CompletedTreatmentGullain Barre Syndrome1
2CompletedTreatmentParoxysmal Nocturnal Haemoglobinuria (PNH)2
2CompletedTreatmentStage V Chronic Kidney Disease1
2RecruitingPreventionDiabetes Mellitus (DM)1
2RecruitingPreventionEnd-Stage Renal Disease (ESRD) / Graft Reperfusion Injury / Renal Failure1
2TerminatedTreatmentAntibody Mediated Rejection1
2TerminatedTreatmentAntibody-mediated Rejection / Humoral Rejection1
2TerminatedTreatmentMyasthenia Gravis1
2Unknown StatusPreventionDelayed Function of Renal Transplant1
2Unknown StatusTreatmentGullian Barre Syndrome1
2WithdrawnTreatmentAnti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis1
2, 3CompletedPreventionDelayed Graft Function1
2, 3CompletedTreatmentShiga-like Toxin-producing Escherichia Coli1
3Active Not RecruitingTreatmentNeuromyelitis Optica / Neuromyelitis Optica Spectrum Disorder1
3Active Not RecruitingTreatmentParoxysmal Nocturnal Haemoglobinuria (PNH)1
3Active Not RecruitingTreatmentRefractory Generalized Myasthenia Gravis1
3Approved for MarketingNot AvailableParoxysmal Hemoglobinuria1
3CompletedEducational/Counseling/TrainingParoxysmal Hemoglobinuria1
3CompletedPreventionLeukemias1
3CompletedTreatmentParoxysmal Hemoglobinuria2
3CompletedTreatmentParoxysmal Hemoglobinuria, Nocturnal2
3CompletedTreatmentRefractory Generalized Myasthenia Gravis1
3Enrolling by InvitationTreatmentNeuromyelitis Optica / Neuromyelitis Optica Spectrum Disorder1
3RecruitingTreatmentAdult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Who Are Currently Being Treated With Eculizumab / Paroxysmal Nocturnal Haemoglobinuria (PNH)1
3RecruitingTreatmentHemolytic Uremic Syndrome of Childhood1
4CompletedTreatmentParoxysmal Hemoglobinuria1
4Enrolling by InvitationTreatmentAntibody-mediated Rejection / Cardiac Allograft Vasculopathy / Heart Graft Dysfunction / Hyperacute Rejection of Cardiac Transplant / Symptomatic left ventricular ejection fraction ≤ 35% Chronic heart failure1
4RecruitingTreatmentAtypical Hemolytic Uremic Syndrome (aHUS)1
Not AvailableActive Not RecruitingTreatmentTransplant, Kidney1
Not AvailableRecruitingNot AvailableDisorder Related to Bone Marrow Transplantation / Thrombotic Microangiopathies1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Dosage forms
FormRouteStrength
Injection, solution, concentrateIntravenous300 mg
Injection, solution, concentrateIntravenous300 mg/30mL
SolutionIntravenous10 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)
CA2189015No2010-04-132015-04-30Canada

Properties

State
Liquid
Experimental Properties
Not Available

Taxonomy

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

Targets

Kind
Protein
Organism
Human
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. [PubMed:17139284]
  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. [PubMed:17016423]
  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. [PubMed:19399743]
  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 . [PubMed:20011245]
  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. [PubMed:18784156]
  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. [PubMed:17989688]
  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. [PubMed:20378572]
  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. [PubMed:16990386]
  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. [PubMed:17702897]
  10. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Drug created on May 16, 2007 10:57 / Updated on November 19, 2017 20:34