Which medications in the drug class CFTR Potentiators and Correctors are used in the treatment of Cystic Fibrosis?

Updated: Oct 30, 2018
  • Author: Girish D Sharma, MD, FCCP, FAAP; Chief Editor: Kenan Haver, MD  more...
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Answer

CFTR Potentiators and Correctors

Cystic fibrosis transmembrane conductance regulator (CFTR) potentiators are the first available treatment that targets the defective CFTR protein, which is the underlying cause of cystic fibrosis.

CFTR correctors (eg, lumacaftor, tezacaftor) corrects the processing and trafficking defect of the F508del-CFTR protein to enable it to reach the cell surface where the CFTR potentiator, ivacaftor, can further enhance the ion channel function of the CFTR protein.

A recently published phase 3 extension study reported 42% slower rate of decline in percent predicted FEV1 in patients receiving long term treatment with lumacaftor and ivacaftor than in matched CF registry controls. [73]

Similarly, phase 3 trials with tezacaftor/ivacaftor and ivacaftor measured improvements across multiple disease measures, including lung function and pulmonary exacerbations compared with ivacaftor monotherapy. [80, 81]

Ivacaftor (Kalydeco)

Ivacaftor potentiates the CFTR protein, a chloride channel present at the surface of epithelial cells in multiple organs. This facilitates increased chloride transport by potentiating the channel-open probability (or gating) of certain CFTR gene mutations. It is indicated for cystic fibrosis in adults and children aged 12 months or older who have one mutation in the CFTR gene. It is not effective when used without a CFTR corrector (eg, lumacaftor) if the patient is homozygous for the F508del mutation in the CFTR gene.

CFTR gene mutations that produce CFTR protein and are responsive to ivacaftor include:

A455E, A1067T

D110E, D110H, D579G, D1152H, D1270N

E56K, E831X, E193K

F1052V, F1074L

G178R, G551D, G551S, G1069R, G1244E, G1349D

K1060T

L206W

P67L

R74W, R117C, R117H, R347H, R352Q, R1070Q, R1070W

S549N, S549R, S945L, S977F, S1251N, S1255P

711+3A→G, 2789+5G→A, 3272-26A→G, 3849+10κβC→T

Lumacaftor/ivacaftor (Orkambi)

This combination product contains lumacaftor, a CFTR corrector. Lumacaftor corrects the processing and trafficking defect of the F508del-CFTR protein to enable it to reach the cell surface where the CFTR potentiator, ivacaftor, can further enhance the ion channel function of the CFTR protein. Ivacaftor facilitates increased chloride transport by potentiating the channel-open probability (or gating) of the CFTR proteins. The combination is indicated for cystic fibrosis (CF) in patients aged 6 y or older who are homozygous for the F508del mutation in the CFTR gene. This combination is well tolerated in young children. 

Tezacaftor/ivacaftor (Symdeko)

CFTR corrector and potentiator combination regimen. It is indicated for cystic fibrosis (CF) in patients aged ≥12 yr who are homozygous for the F508del mutation or who have at least 1 mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that is responsive to tezacaftor/ivacaftor based on in vitro data and/or clinical evidence.


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