Orkambi is an oral medication developed by Massachusetts-based Vertex Pharmaceuticals and approved by the U.S. Food and Drug Administration (FDA) to treat cystic fibrosis patients ages 6 and older.

Cystic fibrosis is a genetic disease where patients produce too much thick, sticky mucus that damages many organs, particularly the lungs and digestive tract. The amount and thickness of the mucus are controlled by chloride channels, which are cell proteins that help move salts and water across cells membranes. Patients with cystic fibrosis have a mutation in the CFTR gene, causing them to have faulty chloride channel proteins.

How Orkambi works

Orkambi is a combination of two compounds — lumacaftor and ivacaftor (FDA-approved in 2012 for the treatment of cystic fibrosis and marketed as Kalydeco). These compounds target the defective chloride channel. Lumacaftor increases the amount of this channel on cell surfaces, while ivacaftor helps defective channels work better. Together, they maintain the balance between salt and water, keeping mucus from clogging the ducts of organs.

Everyone inherits two copies of the CFTR gene — one from each parent. There are over 1,700 mutations that have been found in the CFTR gene. Orkambi works for those with two copies of the F508del variant of the CFTR mutation, the most common mutation in patients with cystic fibrosis worldwide.

Orkambi in clinical trials

Orkambi was initially approved in 2015 for patients, ages 12 and above, based on the results of three Phase 3 clinical trials:  TRAFFIC (NCT01807923), TRANSPORT (NCT01807949), and PROGRESS (NCT01931839). The TRAFFIC and TRANSPORT studies collectively looked at 1,108 cystic fibrosis patients with two copies of the F508del mutation and found that patients who took either 400 mg or 600 mg of lumacaftor plus 250 mg of ivacaftor every morning (combo tablet) and another 250 mg of ivacaftor  at night for six months had much better lung function, fewer hospital admissions, and lower antibiotic usage.

Patients were then invited to the extension PROGRESS trial, continuing on the same dosages they were assigned to in TRAFFIC and TRANSPORT — with those in placebo groups moving to 600 mg of lumacaftor plus 250 mg of ivacaftor every morning plus ivacaftor at night — and evaluated for two years. The PROGRESS study confirmed that long-term Orkambi usage could also improve lung function, maintain patients’ body-mass index (a measure of body weight for height), and was safe and tolerable.

In 2016, FDA approval for Orkambi was expanded to include CF patients ages 6 to 11 with two copies of the F508del mutation, a decision that allows an estimated 2,400 more children in the U.S. to benefit from this treatment. Two Phase 3 clinical trials (NCT01897233 and NCT02514473) were carried out in patients in this age group. In both, treatment-group patients were given 200 mg lumacaftor and 250 mg ivacaftor every 12 hours for six months. Like in previous studies, children in these trials showed improvements in lung function, and Orkambi’s use was safe and tolerable.

Vertex is looking to expand access to patients ages 2 to 5. An open-label Phase 3 clinical trial (NCT02797132) that investigated lumacaftor (100 mg and 150 mg doses) and ivacaftor (125 mg and 188 mg doses) given to 60 children every 12 hours for six months was completed in September 2017.

Other details 

Orkambi is available as single-pill tablets containing dosages of either lumacaftor 100 mg/ivacaftor 125 mg (patients ages 6 to 12) or lumacaftor 200 mg/ivacaftor 125mg (ages 12 and older). Orkambi should be taken every 12 hours with fat-containing foods, such dairy products, nuts, and avocados, as fat helps the body better absorb the medication.

The most common side effects associated with Orkambi use include breathing problems or chest tightness, nausea, diarrhea, stomach discomfort, cold symptoms (a sore throat and runny nose), fatigue, rash, or irregular menstrual periods. Children may experience headaches, stuffy noses, stomach pain, and an increase in the amount of phlegm.

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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.

8 comments

    • 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.

    • jake says:

      this has just been accepted on the pbs in aus, pharmaceutical benefits scheme, if its safe here the research has been done. apparently the drug was around the $250,000 mark here reduced down to $10, if the govt subsidises it then there is a legit reason why.

  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

    • Shirley Jorissen says:

      My wife has scarred lungs. She is eighty years old and is in reasonable good health. She gets out of breath quickly even after walking ten or twenty metres. She is on a Everflo concentrator when she needs to. Would you suggest we talk to our doctor at the sleep order clinic in Perth Western Australia, regarding the new drug made available , called Orkambi ?

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