avacopan 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
complement receptor antagonists or complement inhibitors 5494 1346623-17-3

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • avacopan
  • tavneos
  • CCX168
Avacopan is a complement 5a receptor (C5aR) antagonist that inhibits the interaction between C5aR and the anaphylatoxin C5a. Avacopan blocks C5a-mediated neutrophil activation and migration. The precise mechanism by which avacopan exerts a therapeutic effect in patients with ANCA-associated vasculitis has not been definitively established.
  • Molecular weight: 581.66
  • Formula: C33H35F4N3O2
  • CLOGP: 7.62
  • LIPINSKI: 2
  • HAC: 5
  • HDO: 2
  • TPSA: 61.44
  • ALOGS: -6.42
  • ROTB: 7
  • Status: ONP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
60 mg O

ADMET properties:

None

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 4.826 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 2.904 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 1.230 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 26.607 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 0.280 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 0.280 % High 1
herg hERG pIC50 4.910 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 17.219 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 97.499 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 0.300 % High 1
kinase-safety-class ACVR2B,BRAF,CDK5,EIF2AK3,GRK2,ITK,MAPK10,MAPKAPK2,MET,PDK1,PDK2,PDK4 12
kinase-selectivity-class AXL,GRK2,PDK4 3
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 0.637 High 1
mh-clint Mouse hepatocyte intrinsic clearance 57.148 High 1
mppb Mouse plasma protein binding (% unbound) 0.260 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 2.951 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 1
pppb Pig plasma protein binding (% unbound) 0.300 % High 1
rh-clint Rat hepatocyte intrinsic clearance 47.863 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 0.600 % High 1
rppb Rat plasma protein binding (% unbound) 0.270 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 1.023 uM High 1

Approvals:

DateAgencyCompanyOrphan
Oct. 7, 2021 FDA CHEMOCENTRYX
Sept. 27, 2021 PMDA KISSEI PHARMACEUTICAL CO., LTD.
Jan. 11, 2022 EMA Vifor Fresenius Medical Care Renal Pharma France

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Hospitalisation 191.95 27.81 83 2178 128017 90498169
Drug-induced liver injury 130.07 27.81 57 2204 90261 90535925
Vanishing bile duct syndrome 126.89 27.81 23 2238 1349 90624837
Jaundice 97.83 27.81 35 2226 32482 90593704
Hepatic function abnormal 96.22 27.81 38 2223 46250 90579936
Liver disorder 85.38 27.81 47 2214 121222 90504964
Cytomegalovirus infection 81.38 27.81 29 2232 26573 90599613
Intentional underdose 64.67 27.81 14 2247 2035 90624151
Dialysis 57.12 27.81 18 2243 11311 90614875
Raoultella ornithinolytica infection 56.14 27.81 8 2253 98 90626088
Pneumocystis jirovecii pneumonia 52.89 27.81 20 2241 21596 90604590
Off label use 52.58 27.81 96 2165 1102156 89524030
Therapy interrupted 51.27 27.81 25 2236 50083 90576103
Pneumonia bacterial 50.96 27.81 17 2244 12773 90613413
Death 45.02 27.81 56 2205 456495 90169691
COVID-19 39.33 27.81 33 2228 168810 90457376
Serratia infection 37.55 27.81 8 2253 1077 90625109
Pseudomonas infection 33.65 27.81 13 2248 14852 90611334
Cholestasis 30.90 27.81 16 2245 36283 90589903
Neutropenia 29.48 27.81 32 2229 224872 90401314
Vasculitis 28.34 27.81 13 2248 22680 90603506

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Hospitalisation 201.48 33.66 82 1489 74248 42545516
Intentional underdose 54.91 33.66 11 1560 739 42619025
Drug-induced liver injury 51.37 33.66 26 1545 38247 42581517
Vanishing bile duct syndrome 50.02 33.66 12 1559 1859 42617905
Underdose 46.93 33.66 19 1552 16647 42603117
Liver disorder 44.79 33.66 24 1547 39620 42580144
Dialysis 41.95 33.66 16 1555 11970 42607794
COVID-19 34.93 33.66 31 1540 115917 42503847

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Hospitalisation 386.58 28.23 155 3691 142338 110443115
Vanishing bile duct syndrome 166.91 28.23 35 3811 3133 110582320
Drug-induced liver injury 158.18 28.23 79 3767 119988 110465465
Liver disorder 123.66 28.23 71 3775 142172 110443281
Hepatic function abnormal 118.23 28.23 59 3787 89236 110496217
Intentional underdose 116.19 28.23 25 3821 2527 110582926
Jaundice 111.82 28.23 50 3796 59186 110526267
Dialysis 84.30 28.23 30 3816 19589 110565864
Pneumocystis jirovecii pneumonia 80.38 28.23 36 3810 42699 110542754
Pneumonia bacterial 75.78 28.23 30 3816 26231 110559222
Therapy interrupted 72.08 28.23 35 3811 49787 110535666
COVID-19 69.93 28.23 62 3784 244998 110340455
Cytomegalovirus infection 63.34 28.23 33 3813 54411 110531042
Off label use 62.94 28.23 151 3695 1500034 109085419
Underdose 55.85 28.23 32 3814 63522 110521931
Death 55.37 28.23 92 3754 698777 109886676
Cholestasis 50.14 28.23 30 3816 64488 110520965
Raoultella ornithinolytica infection 49.02 28.23 8 3838 177 110585276
Anti-neutrophil cytoplasmic antibody positive vasculitis 46.53 28.23 14 3832 5403 110580050
Mixed liver injury 46.37 28.23 17 3829 12062 110573391
Vasculitis 39.59 28.23 21 3825 35852 110549601
Glomerulonephritis rapidly progressive 33.93 28.23 9 3837 2206 110583247
Tracheal stenosis 33.17 28.23 7 3839 644 110584809
Steroid diabetes 30.22 28.23 10 3836 5244 110580209
Serratia infection 29.07 28.23 8 3838 2251 110583202

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L04AJ05 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
IMMUNOSUPPRESSANTS
IMMUNOSUPPRESSANTS
Complement inhibitors
FDA MoA N0000182141 Cytochrome P450 3A4 Inhibitors
FDA EPC N0000193973 Complement 5a Receptor Antagonist
FDA MoA N0000193974 Complement 5a Receptor Antagonists

Related Drugs by ATC class:

L04AJ Complement inhibitors 10 drugs
crovalimab-akkzdanicopaneculizumabiptacopanpegcetacoplanpozelimabravulizumabsutimlimabvilobelimabzilucoplan

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Granulomatosis with polyangiitis indication 195353004 DOID:12132
Anti-Neutrophil Cytoplasmic Autoantibody (ANCA)-associated vasculitis (granulomatosis with polyangiitis and microscopic polyangiitis) indication 722191003
Microscopic polyangiitis indication 1144805008




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

None

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
10MG TAVNEOS CHEMOCENTRYX N214487 Oct. 7, 2021 RX CAPSULE ORAL 11603356 Nov. 27, 2039 AN ADJUNCTIVE TREATMENT OF ADULT PATIENTS WITH TAVNEOS (AVACOPAN) WITH SEVERE ACTIVE ANCA-ASSOCIATED VASCULITIS (GPA AND MPA) IN COMBINATION WITH STANDARD THERAPY INCLUDING GLUCOCORTICOIDS

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
10MG TAVNEOS CHEMOCENTRYX N214487 Oct. 7, 2021 RX CAPSULE ORAL Oct. 7, 2026 NEW CHEMICAL ENTITY
10MG TAVNEOS CHEMOCENTRYX N214487 Oct. 7, 2021 RX CAPSULE ORAL Oct. 7, 2028 AS AN ADJUNCTIVE TREATMENT OF ADULT PATIENTS WITH SEVERE ACTIVE ANTI-NEUTROPHIL CYTOPLASMIC AUTOANTIBODY (ANCA)-ASSOCIATED VASCULITIS (GRANULOMATOSIS WITH POLYANGIITIS [GPA] AND MICROSCOPIC POLYANGIITIS [MPA])

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
C5a anaphylatoxin chemotactic receptor 1 GPCR ANTAGONIST IC50 9.35 DRUG LABEL DRUG LABEL

External reference:

IDSource
CHEBI:756375 CHEBI
EFD PDB_CHEM_ID
CHEMBL3989871 ChEMBL_ID
C000620232 MESH_SUPPLEMENTAL_RECORD_UI
9450 IUPHAR_LIGAND_ID
DB15011 DRUGBANK_ID
1264265006 SNOMEDCT_US
1264467000 SNOMEDCT_US
4040886 VANDF
C4507514 UMLSCUI
D11093 KEGG_DRUG
10211 INN_ID
49841217 PUBCHEM_CID
351739 MMSL
39994 MMSL
d09819 MMSL
018869 NDDF
O880NM097T UNII
2572100 RXNORM
O880NM097T INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
TAVNEOS HUMAN PRESCRIPTION DRUG LABEL 1 73556-168 CAPSULE 10 mg ORAL NDA 31 sections