Orkambi is an oral medication developed by Massachusetts-based Vertex Pharmaceuticals and approved by the U.S. Food and Drug Administration (FDA) to treat patients, ages 2 and older, with cystic fibrosis caused by a common mutation.

Cystic fibrosis is a genetic disease where patients produce too much thick, sticky mucus that damages numerous organs, but particularly the lungs and digestive tract. The amount and thickness of the mucus are controlled by chloride channels, which are cellular proteins that help move salts and water across cell membranes. Patients with cystic fibrosis have one or more mutations in the CFTR gene that affects the workings of chloride channel proteins.

How Orkambi works

Orkambi is a combination of two compounds — lumacaftor and ivacaftor (the latter FDA-approved in 2012 to treat cystic fibrosis patients with rarer mutations and marketed as Kalydeco). These compounds target the defective chloride channels. 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 each gene, including the CFTR gene. More than 1,700 mutations have been found in the CFTR gene. Orkambi works for patients with the F508del mutation in both copies the CFTR gene, the most common mutation in people with cystic fibrosis worldwide.

Orkambi in clinical trials

Orkambi was initially approved by the FDA in 2015 for patients ages 12 and older, based on the results of three Phase 3 clinical trials:  TRAFFIC (NCT01807923), TRANSPORT (NCT01807949), and PROGRESS (NCT01931839). The TRAFFIC and TRANSPORT trials collectively looked at 1,108 cystic fibrosis patients with two copies of the F508del mutation and found that patients taking either 400 mg or 600 mg of lumacaftor plus 250 mg of ivacaftor every morning (as a 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 than placebo.

Patients were then invited to the extension PROGRESS trial, continuing on the same dosages assigned 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. Results from the PROGRESS study confirmed that long-term Orkambi use could also improve lung function, maintain a healthier body-mass index (a measure of body weight for height), and was safe and well-tolerated.

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

Orkambi’s label was extended to toddlers and young children with two F508del mutations (ages 2 through 5) in August 2018, based on the results of an open-label Phase 3 clinical trial (NCT02797132) that investigated lumacaftor (at 100 mg and 150 mg doses) and ivacaftor (at 125 mg and 188 mg doses). A total of 60 children were treated every 12 hours for six months. The treatment was well-tolerated; patients showed benefits and responses similar to that of older children in earlier studies. The most common side effect reported was cough, which affected 63 percent of these young children. 

Orkambi is also approved to treat children and adults with cystic fibrosis and two F508del mutations across the European Union, and in Australia and Canada.

Other details 

Orkambi is available as tablets or as granules (for 2–5 year olds) with doses of lumacaftor at 100 mg and ivacaftor at 125 mg for patients weighing less than 31 pounds/14 kilograms, or lumacaftor at 150 mg and ivacaftor at 188mg for patients weighing 31 pounds/14 kilograms or more. Orkambi should be taken every 12 hours with fat-containing foods, such as 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 such as a sore throat and runny nose, fatigue, rash, or irregular menstrual periods. Children may experience headaches, a stuffy nose, 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.

Patrícia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.
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Patrícia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.