The most prevalent form of cystic fibrosis arises from an amino acid deletion in the cystic fibrosis transmembrane conductance regulator, CFTR. A recently approved treatment for individuals homozygous for this mutation combines a chemical corrector, which helps CFTR fold, and a potentiator that increases CFTR channel activity.
NAME
Orkambi, a combination of VX-809 (Lumacaftor) and VX-770 (Ivacaftor)
APPROVED FOR
Cystic fibrosis (CF) in patients older than 12 with two copies of the ΔF508 CFTR gene
TYPE
Small-molecules
MOLECULAR TARGETS
CFTR, an anion channel in the ATP binding cassette transporter family
CELLULAR TARGETS
Various epithelial tissues in which CFTR regulates chloride, bicarbonate, and fluid secretion
EFFECTS ON TARGETS
Lumacaftor corrects mutant CFTR folding, and Ivacaftor potentiates CFTR channel activity. Restored CFTR trafficking and activity counters the fluid secretion defects in pancreas, intestine, sweat glands, and lung, where it improves airway surface liquid formation and productive mucus and microbe clearance.
DEVELOPED BY
Vertex Pharmaceuticals and Cystic Fibrosis Foundation Therapeutics
