Details
Stereochemistry | ACHIRAL |
Molecular Formula | C24H18F2N2O5 |
Molecular Weight | 452.4069 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CC1=CC=C(NC(=O)C2(CC2)C3=CC4=C(OC(F)(F)O4)C=C3)N=C1C5=CC=CC(=C5)C(O)=O
InChI
InChIKey=UFSKUSARDNFIRC-UHFFFAOYSA-N
InChI=1S/C24H18F2N2O5/c1-13-5-8-19(27-20(13)14-3-2-4-15(11-14)21(29)30)28-22(31)23(9-10-23)16-6-7-17-18(12-16)33-24(25,26)32-17/h2-8,11-12H,9-10H2,1H3,(H,29,30)(H,27,28,31)
DescriptionSources: http://adisinsight.springer.com/drugs/800027666Curator's Comment: Description was created based on several sources, including
http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206038Orig1s000lbl.pdf
https://newdrugapprovals.org/tag/lumacaftor/
Sources: http://adisinsight.springer.com/drugs/800027666
Curator's Comment: Description was created based on several sources, including
http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206038Orig1s000lbl.pdf
https://newdrugapprovals.org/tag/lumacaftor/
Lumacaftor (VX-809) is an investigational drug developed by the Massachusetts-based pharmaceutical company Vertex for the treatment of patients who suffer from cystic fibrosis (CF) and have the F508del mutation in the CF transmembrane conductance regulator (CFTR). Currently, lumacaftor is approved by the U.S. FDA as a combined oral treatment for CF in combination with Kalydeco (ivacaftor). Lumacaftor is commercialized by Vertex under the brand name Orkambi, and Kalydeco was approved in the United States in 2012. The lumacaftor/Kalydeco combo was approved by the FDA in July 2015 for patients ages 12 and older, while the use of lumacaftor alone is still being studied by Vertex. The mechanism of action of lumacaftor is based on the interference with the F508 CFTR. The chronic disease is caused by a mutation in the gene that controls the salt transportation in the cells, resulting in thick, sticky mucus in the respiratory, digestive, and reproductive systems. To address that genetic defect, lumacaftor helps correct the mutated genes with a novel therapeutic approach. Both lumicaftor and kalydeco work by correcting the misfolded CFTR protein, the root cause of the F508del mutation, which led to the approval of the combined treatment by the FDA. However, while kalydeco alone is also approved by the FDA, the use of lumacftor alone has not yet been approved.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: F508del-CFTR |
|||
Target ID: CHEMBL2364675 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27821435 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Orkambi Approved UseORKAMBI is a combination of lumacaftor and ivacaftor, a cystic fibrosis
transmembrane conductance regulator (CFTR) potentiator, indicated for the
treatment of cystic fibrosis (CF) in patients age 12 years and older who are
homozygous for the F508del mutation in the CFTR gene. If the patient’s
genotype is unknown, an FDA-cleared CF mutation test should be used to detect
the presence of the F508del mutation on both alleles of the CFTR gene. Launch Date2015 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
25 μg/mL |
400 mg 2 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
LUMACAFTOR plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
198 μg × h/mL |
400 mg 2 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
LUMACAFTOR plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
25.2 h |
200 mg 2 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
LUMACAFTOR plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1% |
400 mg 2 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
LUMACAFTOR plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
200 mg 1 times / day steady, oral Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy, 25 years(range: 18–42 years) n = 19 Health Status: unhealthy Age Group: 25 years(range: 18–42 years) Sex: M+F Population Size: 19 Sources: |
Other AEs: Cough, Headache... Other AEs: Cough (52.6%) Sources: Headache (26.3%) Rales (15.8%) Productive cough (31.6%) Dyspnoea (21.1%) Respiratory tract disorders NEC (21.1%) Fatigue (15.8%) Fever (26.3%) Nasal congestion (11.8%) Oropharyngeal pain (10.5%) Sinus congestion (5.3%) Respiration abnormal (21.1%) Haemoptysis (10.5%) Constipation (5.3%) Abdominal pain (5.3%) Myalgia (5.3%) Post-tussive vomiting (5.3%) Nausea (5.3%) Nasopharyngitis (10.5%) Dizziness (5.3%) Back pain (5.3%) Abdominal pain upper (10.5%) Sputum abnormal (5.3%) Epistaxis (10.5%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Abdominal pain upper | 10.5% | 200 mg 1 times / day steady, oral Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy, 25 years(range: 18–42 years) n = 19 Health Status: unhealthy Age Group: 25 years(range: 18–42 years) Sex: M+F Population Size: 19 Sources: |
Epistaxis | 10.5% | 200 mg 1 times / day steady, oral Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy, 25 years(range: 18–42 years) n = 19 Health Status: unhealthy Age Group: 25 years(range: 18–42 years) Sex: M+F Population Size: 19 Sources: |
Haemoptysis | 10.5% | 200 mg 1 times / day steady, oral Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy, 25 years(range: 18–42 years) n = 19 Health Status: unhealthy Age Group: 25 years(range: 18–42 years) Sex: M+F Population Size: 19 Sources: |
Nasopharyngitis | 10.5% | 200 mg 1 times / day steady, oral Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy, 25 years(range: 18–42 years) n = 19 Health Status: unhealthy Age Group: 25 years(range: 18–42 years) Sex: M+F Population Size: 19 Sources: |
Oropharyngeal pain | 10.5% | 200 mg 1 times / day steady, oral Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy, 25 years(range: 18–42 years) n = 19 Health Status: unhealthy Age Group: 25 years(range: 18–42 years) Sex: M+F Population Size: 19 Sources: |
Nasal congestion | 11.8% | 200 mg 1 times / day steady, oral Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy, 25 years(range: 18–42 years) n = 19 Health Status: unhealthy Age Group: 25 years(range: 18–42 years) Sex: M+F Population Size: 19 Sources: |
Fatigue | 15.8% | 200 mg 1 times / day steady, oral Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy, 25 years(range: 18–42 years) n = 19 Health Status: unhealthy Age Group: 25 years(range: 18–42 years) Sex: M+F Population Size: 19 Sources: |
Rales | 15.8% | 200 mg 1 times / day steady, oral Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy, 25 years(range: 18–42 years) n = 19 Health Status: unhealthy Age Group: 25 years(range: 18–42 years) Sex: M+F Population Size: 19 Sources: |
Dyspnoea | 21.1% | 200 mg 1 times / day steady, oral Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy, 25 years(range: 18–42 years) n = 19 Health Status: unhealthy Age Group: 25 years(range: 18–42 years) Sex: M+F Population Size: 19 Sources: |
Respiration abnormal | 21.1% | 200 mg 1 times / day steady, oral Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy, 25 years(range: 18–42 years) n = 19 Health Status: unhealthy Age Group: 25 years(range: 18–42 years) Sex: M+F Population Size: 19 Sources: |
Respiratory tract disorders NEC | 21.1% | 200 mg 1 times / day steady, oral Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy, 25 years(range: 18–42 years) n = 19 Health Status: unhealthy Age Group: 25 years(range: 18–42 years) Sex: M+F Population Size: 19 Sources: |
Fever | 26.3% | 200 mg 1 times / day steady, oral Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy, 25 years(range: 18–42 years) n = 19 Health Status: unhealthy Age Group: 25 years(range: 18–42 years) Sex: M+F Population Size: 19 Sources: |
Headache | 26.3% | 200 mg 1 times / day steady, oral Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy, 25 years(range: 18–42 years) n = 19 Health Status: unhealthy Age Group: 25 years(range: 18–42 years) Sex: M+F Population Size: 19 Sources: |
Productive cough | 31.6% | 200 mg 1 times / day steady, oral Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy, 25 years(range: 18–42 years) n = 19 Health Status: unhealthy Age Group: 25 years(range: 18–42 years) Sex: M+F Population Size: 19 Sources: |
Abdominal pain | 5.3% | 200 mg 1 times / day steady, oral Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy, 25 years(range: 18–42 years) n = 19 Health Status: unhealthy Age Group: 25 years(range: 18–42 years) Sex: M+F Population Size: 19 Sources: |
Back pain | 5.3% | 200 mg 1 times / day steady, oral Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy, 25 years(range: 18–42 years) n = 19 Health Status: unhealthy Age Group: 25 years(range: 18–42 years) Sex: M+F Population Size: 19 Sources: |
Constipation | 5.3% | 200 mg 1 times / day steady, oral Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy, 25 years(range: 18–42 years) n = 19 Health Status: unhealthy Age Group: 25 years(range: 18–42 years) Sex: M+F Population Size: 19 Sources: |
Dizziness | 5.3% | 200 mg 1 times / day steady, oral Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy, 25 years(range: 18–42 years) n = 19 Health Status: unhealthy Age Group: 25 years(range: 18–42 years) Sex: M+F Population Size: 19 Sources: |
Myalgia | 5.3% | 200 mg 1 times / day steady, oral Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy, 25 years(range: 18–42 years) n = 19 Health Status: unhealthy Age Group: 25 years(range: 18–42 years) Sex: M+F Population Size: 19 Sources: |
Nausea | 5.3% | 200 mg 1 times / day steady, oral Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy, 25 years(range: 18–42 years) n = 19 Health Status: unhealthy Age Group: 25 years(range: 18–42 years) Sex: M+F Population Size: 19 Sources: |
Post-tussive vomiting | 5.3% | 200 mg 1 times / day steady, oral Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy, 25 years(range: 18–42 years) n = 19 Health Status: unhealthy Age Group: 25 years(range: 18–42 years) Sex: M+F Population Size: 19 Sources: |
Sinus congestion | 5.3% | 200 mg 1 times / day steady, oral Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy, 25 years(range: 18–42 years) n = 19 Health Status: unhealthy Age Group: 25 years(range: 18–42 years) Sex: M+F Population Size: 19 Sources: |
Sputum abnormal | 5.3% | 200 mg 1 times / day steady, oral Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy, 25 years(range: 18–42 years) n = 19 Health Status: unhealthy Age Group: 25 years(range: 18–42 years) Sex: M+F Population Size: 19 Sources: |
Cough | 52.6% | 200 mg 1 times / day steady, oral Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy, 25 years(range: 18–42 years) n = 19 Health Status: unhealthy Age Group: 25 years(range: 18–42 years) Sex: M+F Population Size: 19 Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 6.0 |
no | |||
Page: 5.0 |
no | |||
Page: 6.0 |
no | |||
Page: 5.0 |
no | |||
Page: 5.0 |
no | |||
Page: 6.0 |
no | |||
no | ||||
no | ||||
Page: 5.0 |
yes | |||
Page: 5.0 |
yes | |||
Page: 5.0 |
yes | |||
Page: 5.0 |
yes | |||
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
no | ||||
no | ||||
yes | ||||
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204153Orig1s000PharmR.pdf#page=4 Page: 4.0 |
PubMed
Title | Date | PubMed |
---|---|---|
VX-809 corrects folding defects in cystic fibrosis transmembrane conductance regulator protein through action on membrane-spanning domain 1. | 2013 Oct |
|
A CFTR corrector (lumacaftor) and a CFTR potentiator (ivacaftor) for treatment of patients with cystic fibrosis who have a phe508del CFTR mutation: a phase 2 randomised controlled trial. | 2014 Jul |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.drugs.com/dosage/orkambi.html
Adults and pediatric patients age 12 years and older: two tablets (each containing lumacaftor 200 mg/ivacaftor 125 mg) taken orally every 12 hours with fat-containing food.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24726831
Acute pretreatment of temperature-rescued F508del-CFTR in BHK Cells with 3uM Lumacaftor (VX-809) promotes channel activation
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Classification Tree | Code System | Code | ||
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FDA ORPHAN DRUG |
301610
Created by
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EMA ASSESSMENT REPORTS |
ORKAMBI (AUTHORIZED: CYSTIC FIBROSIS)
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FDA ORPHAN DRUG |
434814
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EU-Orphan Drug |
EU/3/14/1333
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FDA ORPHAN DRUG |
761720
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WHO-ATC |
R07AX30
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936727-05-8
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N0000184145
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PRIMARY | Chloride Channel Activation Potentiators [MoA] | ||
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EGP8L81APK
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CHEMBL2103870
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5010
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XX-134
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DB09280
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N0000187063
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PRIMARY | Cytochrome P450 2C8 Inducers [MoA] | ||
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N0000187064
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PRIMARY | Cytochrome P450 2B6 Inducers [MoA] | ||
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LUMACAFTOR
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7481
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N0000185504
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PRIMARY | Cytochrome P450 2C9 Inhibitors [MoA] | ||
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N0000185607
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PRIMARY | Cytochrome P450 2C19 Inducers [MoA] | ||
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9449
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m11859
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N0000190118
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PRIMARY | Cytochrome P450 3A Inducers [MoA] | ||
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1655922
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PRIMARY | RxNorm | ||
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SUB130518
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N0000185507
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PRIMARY | Cytochrome P450 2C9 Inducers [MoA] | ||
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90951
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EGP8L81APK
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Lumacaftor and Ivacaftor
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16678941
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DTXSID30239523
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N0000187062
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PRIMARY | Cytochrome P450 2C8 Inhibitors [MoA] | ||
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C170136
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100000156577
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ACTIVE MOIETY