lumacaftor indications/contra

Stem definitionDrug idCAS RN
cystic fibrosis transmembrane regulator (CFTR) protein modulators 5010 936727-05-8

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • lumacaftor
  • VX-809
  • VRT-826809
Lumacaftor improves the conformational stability of F508del-CFTR, resulting in increased processing and trafficking of mature protein to the cell surface.
  • Molecular weight: 452.41
  • Formula: C24H18F2N2O5
  • CLOGP: 6.05
  • LIPINSKI: 1
  • HAC: 7
  • HDO: 2
  • TPSA: 97.75
  • ALOGS: -5.08
  • ROTB: 5

Drug dosage:

None

Approvals:

DateAgencyCompanyOrphan
July 2, 2015 FDA VERTEX PHARMS INC

FDA Adverse Event Reporting System

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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
Infective pulmonary exacerbation of cystic fibrosis 1971.55 69.00 248 1220 297 3384094
Hospitalisation 674.87 69.00 172 1296 20553 3363838
Respiration abnormal 497.87 69.00 77 1391 624 3383767
Cystic fibrosis 369.59 69.00 58 1410 518 3383873
Dyspnoea 360.61 69.00 159 1309 102775 3281616
Chest discomfort 304.48 69.00 89 1379 17196 3367195
Pulmonary function test decreased 269.50 69.00 45 1423 608 3383783
Forced expiratory volume decreased 268.17 69.00 44 1424 530 3383861
Sputum increased 129.58 69.00 21 1447 231 3384160
Cough 126.29 69.00 58 1410 39800 3344591
Drug dose omission 125.13 69.00 57 1411 38375 3346016
Cystic fibrosis respiratory infection suppression 122.74 69.00 15 1453 9 3384382
Haemoptysis 97.76 69.00 30 1438 6701 3377690
Diarrhoea 70.14 69.00 56 1412 104292 3280099
Drug screen false positive 69.18 69.00 14 1454 560 3383831

Pharmacologic Action:

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SourceCodeDescription
ATC R07AX30 RESPIRATORY SYSTEM
OTHER RESPIRATORY SYSTEM PRODUCTS
OTHER RESPIRATORY SYSTEM PRODUCTS
Other respiratory system products
FDA MoA N0000190118 Cytochrome P450 3A Inducers
FDA MoA N0000187064 Cytochrome P450 2B6 Inducers
FDA MoA N0000187063 Cytochrome P450 2C8 Inducers
FDA MoA N0000185507 Cytochrome P450 2C9 Inducers
FDA MoA N0000185607 Cytochrome P450 2C19 Inducers
FDA MoA N0000187062 Cytochrome P450 2C8 Inhibitors
FDA MoA N0000185504 Cytochrome P450 2C9 Inhibitors
FDA MoA N0000191264 P-Glycoprotein Inducers
FDA MoA N0000185503 P-Glycoprotein Inhibitors
CHEBI has role CHEBI:71031 orphan drug

Drug Use (View source of the data)

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DiseaseRelationSNOMED_IDDOID
Cystic fibrosis of the lung indication 86555001

Acid dissociation constants calculated using MoKa v3.0.0

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Dissociation levelDissociation constantType (acidic/basic)
pKa1 4.67 acidic
pKa2 10.91 acidic
pKa3 4.06 Basic

Orange Book patent data (new drug applications)

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Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
100MG ORKAMBI VERTEX PHARMS INC N206038 Sept. 28, 2016 RX TABLET ORAL 7973038 Nov. 8, 2026 METHOD OF TREATING CYSTIC FIBROSIS USING N-(5-HYDROXY-2,4-DITERT-BUTYL-PHENYL)-4-OXO-1H-QUINOLINE-3-CARBOXAMIDE AND 3-(6-(1-2,2-DIFLUOROBENZO[D][1,3]DIOXOL-5-YL) CYCLOPROPANECARBOXAMIDO)-3-METHYLPYRIDIN-2-YL)BENZOIC ACID
100MG ORKAMBI VERTEX PHARMS INC N206038 Sept. 28, 2016 RX TABLET ORAL 8741933 Nov. 8, 2026 METHOD OF TREATING CYSTIC FIBROSIS IN A PATIENT, THE PATIENT HAVING THE F508DEL MUTATION IN CFTR, USING IVACAFTOR AND LUMACAFTOR
200MG ORKAMBI VERTEX PHARMS INC N206038 July 2, 2015 RX TABLET ORAL 7973038 Nov. 8, 2026 METHOD OF TREATING CYSTIC FIBROSIS USING N-(5-HYDROXY-2,4-DITERT-BUTYL-PHENYL)-4-OXO-1H-QUINOLINE-3-CARBOXAMIDE AND 3-(6-(1-2,2-DIFLUOROBENZO[D][1,3]DIOXOL-5-YL) CYCLOPROPANECARBOXAMIDO)-3-METHYLPYRIDIN-2-YL)BENZOIC ACID
200MG ORKAMBI VERTEX PHARMS INC N206038 July 2, 2015 RX TABLET ORAL 8741933 Nov. 8, 2026 METHOD OF TREATING CYSTIC FIBROSIS IN A PATIENT, THE PATIENT HAVING THE F508DEL MUTATION IN CFTR, USING IVACAFTOR AND LUMACAFTOR
200MG ORKAMBI VERTEX PHARMS INC N206038 July 2, 2015 RX TABLET ORAL 8741933 Nov. 8, 2026 METHOD OF TREATING CYSTIC FIBROSIS IN PATIENTS WHO ARE HOMOZYGOUS FOR THE F508DEL MUTATION IN THE CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR (CFTR) GENE
100MG ORKAMBI VERTEX PHARMS INC N206038 Sept. 28, 2016 RX TABLET ORAL 9670163 Dec. 28, 2026 METHOD OF TREATING A PATIENT HAVING CYSTIC FIBROSIS USING IVACAFTOR AND LUMACAFTOR
200MG ORKAMBI VERTEX PHARMS INC N206038 July 2, 2015 RX TABLET ORAL 9670163 Dec. 28, 2026 METHOD OF TREATING A PATIENT HAVING CYSTIC FIBROSIS USING IVACAFTOR AND LUMACAFTOR
100MG ORKAMBI VERTEX PHARMS INC N206038 Sept. 28, 2016 RX TABLET ORAL 8324242 Aug. 5, 2027 METHOD OF TREATING A PATIENT HAVING CYSTIC FIBROSIS USING IVACAFTOR AND LUMACAFTOR
200MG ORKAMBI VERTEX PHARMS INC N206038 July 2, 2015 RX TABLET ORAL 8324242 Aug. 5, 2027 METHOD OF TREATING A PATIENT HAVING CYSTIC FIBROSIS USING IVACAFTOR AND LUMACAFTOR
200MG ORKAMBI VERTEX PHARMS INC N206038 July 2, 2015 RX TABLET ORAL 8324242 Aug. 5, 2027 METHOD OF TREATING CYSTIC FIBROSIS
100MG ORKAMBI VERTEX PHARMS INC N206038 Sept. 28, 2016 RX TABLET ORAL 8846718 Dec. 4, 2028 METHOD OF TREATING CYSTIC FIBROSIS IN A PATIENT, THE PATIENT HAVING THE F508DEL MUTATION IN CFTR, USING IVACAFTOR AND FORM I LUMACAFTOR
100MG ORKAMBI VERTEX PHARMS INC N206038 Sept. 28, 2016 RX TABLET ORAL 9150552 Dec. 4, 2028 METHOD OF TREATING CYSTIC FIBROSIS IN A PATIENT, THE PATIENT HAVING THE F508DEL MUTATION IN CFTR, USING IVACAFTOR AND FORM I LUMACAFTOR
200MG ORKAMBI VERTEX PHARMS INC N206038 July 2, 2015 RX TABLET ORAL 8846718 Dec. 4, 2028 METHOD OF TREATING CYSTIC FIBROSIS IN A PATIENT, THE PATIENT HAVING THE F508DEL MUTATION IN CFTR, USING IVACAFTOR AND FORM I LUMACAFTOR
200MG ORKAMBI VERTEX PHARMS INC N206038 July 2, 2015 RX TABLET ORAL 8846718 Dec. 4, 2028 METHOD OF TREATING CYSTIC FIBROSIS IN PATIENTS WHO ARE HOMOZYGOUS FOR THE F508DEL MUTATION IN THE CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR (CFTR) GENE
200MG ORKAMBI VERTEX PHARMS INC N206038 July 2, 2015 RX TABLET ORAL 9150552 Dec. 4, 2028 METHOD OF TREATING CYSTIC FIBROSIS IN A PATIENT, THE PATIENT HAVING THE F508DEL MUTATION IN CFTR, USING IVACAFTOR AND FORM I LUMACAFTOR
100MG ORKAMBI VERTEX PHARMS INC N206038 Sept. 28, 2016 RX TABLET ORAL 9192606 Sept. 29, 2029 METHOD OF TREATING CYSTIC FIBROSIS IN A PATIENT, THE PATIENT HAVING THE F508DEL MUTATION IN CFTR, USING A DOSAGE UNIT AS DEFINED IN CLAIM 1 OF U.S. PATENT NO. 9,192,606
200MG ORKAMBI VERTEX PHARMS INC N206038 July 2, 2015 RX TABLET ORAL 9192606 Sept. 29, 2029 METHOD OF TREATING CYSTIC FIBROSIS IN A PATIENT, THE PATIENT HAVING THE F508DEL MUTATION IN CFTR, USING A DOSAGE UNIT AS DEFINED IN CLAIM 1 OF U.S. PATENT NO. 9,192,606
100MG ORKAMBI VERTEX PHARMS INC N206038 Sept. 28, 2016 RX TABLET ORAL 8716338 Sept. 20, 2030 METHOD OF TREATING CYSTIC FIBROSIS IN A PATIENT, THE PATIENT HAVING THE F508DEL MUTATION IN CFTR, USING THE DOSAGE UNIT OF CLAIM 1 OF U.S. PATENT NO. 8,716,338
200MG ORKAMBI VERTEX PHARMS INC N206038 July 2, 2015 RX TABLET ORAL 8716338 Sept. 20, 2030 METHOD OF TREATING CYSTIC FIBROSIS IN A PATIENT, THE PATIENT HAVING THE F508DEL MUTATION IN CFTR, USING THE DOSAGE UNIT OF CLAIM 1 OF U.S. PATENT NO. 8,716,338
200MG ORKAMBI VERTEX PHARMS INC N206038 July 2, 2015 RX TABLET ORAL 8716338 Sept. 20, 2030 METHOD OF TREATING CYSTIC FIBROSIS IN PATIENTS WHO HAVE THE F508DEL MUTATION IN THE CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR (CFTR) GENE.

Orange Book exclusivity data (new drug applications)

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Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
100MG ORKAMBI VERTEX PHARMS INC N206038 Sept. 28, 2016 RX TABLET ORAL Sept. 28, 2019 NEW PATIENT POPULATION
100MG ORKAMBI VERTEX PHARMS INC N206038 Sept. 28, 2016 RX TABLET ORAL July 2, 2020 NEW CHEMICAL ENTITY
200MG ORKAMBI VERTEX PHARMS INC N206038 July 2, 2015 RX TABLET ORAL July 2, 2020 NEW CHEMICAL ENTITY
100MG ORKAMBI VERTEX PHARMS INC N206038 Sept. 28, 2016 RX TABLET ORAL Jan. 25, 2021 ADDITIONAL INFORMATION ADDED TO THE PEDIATRIC USE SECTION OF THE LABELING REGARDING A NEW CLINICAL TRIAL IN PATIENTS AGED 6 THROUGH 11 YEARS (TRIAL 4)
200MG ORKAMBI VERTEX PHARMS INC N206038 July 2, 2015 RX TABLET ORAL Jan. 25, 2021 ADDITIONAL INFORMATION ADDED TO THE PEDIATRIC USE SECTION OF THE LABELING REGARDING A NEW CLINICAL TRIAL IN PATIENTS AGED 6 THROUGH 11 YEARS (TRIAL 4)
100MG ORKAMBI VERTEX PHARMS INC N206038 Sept. 28, 2016 RX TABLET ORAL July 2, 2022 TREATMENT OF CYSTIC FIBROSIS IN PATIENTS AGE 12 YEARS AND OLDER WHO ARE HOMOZYGOUS FOR F508DEL MUTATION IN THE CFTR GENE
200MG ORKAMBI VERTEX PHARMS INC N206038 July 2, 2015 RX TABLET ORAL July 2, 2022 TREATMENT OF CYSTIC FIBROSIS IN PATIENTS AGE 12 YEARS AND OLDER WHO ARE HOMOZYGOUS FOR F508DEL MUTATION IN THE CFTR GENE
100MG ORKAMBI VERTEX PHARMS INC N206038 Sept. 28, 2016 RX TABLET ORAL Sept. 28, 2023 TREATMENT OF CYSTIC FIBROSIS (CF) IN PATIENTS AGE 6-11 YEAR OLD WHO ARE HOMOZYGOUS FOR THE F508DEL MUTATION IN THE CFTR GENE
200MG ORKAMBI VERTEX PHARMS INC N206038 July 2, 2015 RX TABLET ORAL Sept. 28, 2023 TREATMENT OF CYSTIC FIBROSIS (CF) IN PATIENTS AGE 6-11 YEAR OLD WHO ARE HOMOZYGOUS FOR THE F508DEL MUTATION IN THE CFTR GENE

Bioactivity Summary:

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TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Cystic fibrosis transmembrane conductance regulator Ion channel PHARMACOLOGICAL CHAPERONE EC50 6.46 SCIENTIFIC LITERATURE DRUG LABEL

External reference:

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IDSource
7481 IUPHAR_LIGAND_ID
D10134 KEGG_DRUG
4034600 VUID
N0000191736 NUI
C3852684 UMLSCUI
1655922 RXNORM
016231 NDDF
4034600 VANDF
31119 MMSL
d08371 MMSL
N0000191736 NDFRT
716073005 SNOMEDCT_US
EGP8L81APK UNII
9449 INN_ID
CHEMBL2103870 ChEMBL_ID
16678941 PUBCHEM_CID
C569105 MESH_SUPPLEMENTAL_RECORD_UI
DB09280 DRUGBANK_ID
CHEBI:90951 CHEBI

Pharmaceutical products:

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ProductCategoryIngredientsNDCFormQuantityRoute MarketingLabel
ORKAMBI HUMAN PRESCRIPTION DRUG LABEL 2 51167-700 TABLET, FILM COATED 100 mg ORAL NDA 19 sections
ORKAMBI HUMAN PRESCRIPTION DRUG LABEL 2 51167-809 TABLET, FILM COATED 200 mg ORAL NDA 19 sections