Identification
NameEculizumab
Accession NumberDB01257
TypeBiotech
GroupsApproved, Investigational
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 structureDb01257
Related Articles
Protein chemical formulaNot Available
Protein average weight148000.0 Da
SequencesNot Available
Synonyms
5G1.1
External IDs Not Available
Product Ingredients Not Available
Approved 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
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Categories
UNIIA3ULP0F556
CAS number219685-50-4
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.

TargetKindPharmacological actionActionsOrganismUniProt ID
Complement C5Proteinyes
antibody
HumanP01031 details
Related Articles
AbsorptionNot Available
Volume of distribution
  • 7.7 L
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half life

272 ± 82 hrs (mean ± SD)

Clearance
  • 22 mL/hr [typical PNH patient weighing 70 kg]
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
BCG vaccineThe therapeutic efficacy of Bcg 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
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 risk or severity of adverse effects can be increased when Eculizumab is combined with G17DT.Investigational
INGN 201The risk or severity of adverse effects can be increased when Eculizumab is combined with INGN 201.Investigational
INGN 225The risk or severity of adverse effects can be increased when Eculizumab is combined with INGN 225.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
RindopepimutThe risk or severity of adverse effects can be increased when Eculizumab is combined with CDX-110.Investigational
RoflumilastRoflumilast may increase the immunosuppressive activities of Eculizumab.Approved
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Eculizumab.Approved
SRP 299The risk or severity of adverse effects can be increased when Eculizumab is combined with SRP 299.Investigational
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Eculizumab.Approved, Investigational
TofacitinibEculizumab may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
TrastuzumabTrastuzumab may increase the neutropenic activities of Eculizumab.Approved, Investigational
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
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
ATC CodesL04AA25 — Eculizumab
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1Unknown StatusTreatmentDense Deposit Disease / Membranoproliferative Glomerulonephritis1
1Unknown StatusTreatmentKidney; Complications, Allograft1
1, 2Active Not RecruitingPreventionTransplant, Kidney1
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 RecruitingTreatmentGullain Barre Syndrome1
2Active Not RecruitingTreatmentMembranoproliferative Glomerulonephritis1
2Active Not RecruitingTreatmentStage V Chronic Kidney Disease1
2CompletedPreventionAsthma, Allergic1
2CompletedTreatmentAge-Related Macular Degeneration (ARMD)1
2CompletedTreatmentAtypical Hemolytic Uremic Syndrome (aHUS)5
2CompletedTreatmentAtypical Hemolytic-Uremic Syndrome2
2CompletedTreatmentCold type haemolytic anaemia1
2CompletedTreatmentParoxysmal Nocturnal Haemoglobinuria (PNH)2
2RecruitingPreventionDiabetes Mellitus (DM)1
2RecruitingPreventionEnd-Stage Renal Disease (ESRD) / Graft Reperfusion Injury / Renal Failure1
2RecruitingTreatmentAlloimmune Platelet Refractoriness / Thrombocytopenias1
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 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
3RecruitingTreatmentNeuromyelitis Optica / Neuromyelitis Optica Spectrum Disorder1
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
ManufacturersNot 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)
CA2189015 No2010-04-132015-04-30Canada
Properties
StateLiquid
Experimental PropertiesNot Available
Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot 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-C6 complex is the foundation upon which the lytic complex is assembled.Derived from proteolytic degradation of complement C5, C5 anaphylatoxin is a mediator of local inflammatory process. Binding to th...
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 August 17, 2016 12:23