Orkambi for CFOrkambi is a combination therapy (ivacaftor/Kalydeco and lumacaftor) approved by the U.S. Food and Drug Administration (FDA) for treatment of cystic fibrosis (CF).  The oral drug helps in correcting the mutated genes in patients with cystic fibrosis — a novel therapeutic approach designed to treat the root cause of cystic fibrosis instead of just the severity of symptoms.

Developed by the Massachusetts-based pharmaceutical company Vertex, Orkambi is approved for use in cystic fibrosis patients age 12 and older with two copies of the F508del mutation in their CFTR gene. The mutation is the leading cause of CF.  FDA approval for the therapy was announced on July 2, 2015.

History of Orkambi

Two pivotal clinical trials conducted by Vertex (TRAFFIC and TRANSPORT) demonstrated that Orkambi, taken as two pills every 12 hours, improved lung function in CF patients compared to placebo, and proved the drug’s safety as well as its efficacy. F508del is a deletion mutation on the cystic fibrosis transmembrane conductance regulator, or CFTR protein, which causes abnormal transport of sodium through membranes, leading to inflammation and mucus buildup in the lungs, digestive track, and elsewhere in the body. This can lead to severe respiratory and digestive problems, and to complications like infections and diabetes.

Positive trial results were published in the New England Journal of Medicine (May 2015) and The Lancet (June 2014) supporting the protective function of Orkambi in reducing pulmonary exacerbation rates, increasing forced expiratory volume (FEV1) and decreasing the mean sweat chloride concentration.

How Orkambi Works

Both ivacaftor and lumacaftor are oral CFTR modulators, which work by correcting the misfolded CFTR protein that results from F508del mutations. The CFTR protein is a chloride channel present at the surface of epithelial cells in multiple organs that, when misfolded, reduces the quantity of the CFTR protein at the cell surface.

Lumacaftor is a CFTR corrector, and aims to increase CFTR function by increasing the trafficking, or movement, of CFTR to the cell surface. Ivacaftor is a CFTR potentiator, aiming to increase the function of defective CFTR proteins by increasing gating activity, or the ability to transport ions across the cell membrane, of CFTR at the cell surface.

Other Details About Orkambi

One possible drawback to Orkambi is that it is directed toward only a specific mutation, whereas there are more than 1,800 mutations associated with CF, according to the Cystic Fibrosis Foundation. Most, however, are rare. The F508del mutation accounts for about half of all CF cases in the U.S., the FDA reported.

The most common side effects associated with Orkambi use include shortness of breath, upper respiratory tract infection, nausea, diarrhea, and rash. Women who took Orkambi also reported menstrual abnormalities, such as increased bleeding. People also under treatment with certain antibiotics, seizure medications, sedative, and immunosuppressants are advised against taking Orkambi. More safety information is available on the Orkambi website set up by Vertex.

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Note: Cystic Fibrosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.


    • Tim Bossie says:

      Hi Floria, thank you for the very important question. We would have to recommend that you ask your doctor and pharmacist about this.

  1. Cara Bewick says:

    Hi i am doing a school project based on the drug orkambi. What information would you class as important? What would you recommend i include? And is there any other information you can give me? Thanks in advance

  2. Saeed says:

    Hello I have a son with cf 11 years.He has deletion in exon 2 of CFTR gene in homozygous form.Im Iranian .We don t have an expert cf clinic.How can be in touch with a cf physician to get guidance?What would you say about this deletion in exon 2?thanks

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