FDA Clears CF Drug Orkambi for Children as Young as Age 2

Megan Brooks


August 08, 2018

The US Food and Drug Administration (FDA) has further expanded the use of the cystic fibrosis (CF) drug Orkambi (Vertex Pharmaceuticals) for children as young as age 2 who have two copies of the F508del mutation in the CF transmembrane conductance regulator (CFTR) gene, the most common cause of the disease, the company has announced.

Orkambi is a fixed-dose oral combination of lumacaftor and ivacaftor (Kalydeco, Vertex). Lumacaftor increases the amount of mature protein at the cell surface by targeting the processing and trafficking defect of the F508del CFTR protein, and ivacaftor enhances the function of the CFTR protein once it reaches the cell surface.

The FDA first approved Orkambi in 2015 for children aged 12 years and older with CF who have two copies of the F508del mutation, making it first drug for CF directed at the underlying cause of the disease for people with this mutation. A year later, the FDA expanded the indication to include children aged 6 to 11 years.

Orkambi has been shown to improve pulmonary function, increase body weight, and decrease the rate of pulmonary exacerbations in patients with CF who have two copies of the F508del mutation

Approval of Orkambi in children as young as age 2 was based on a phase 3 open-label safety study in 60 patients that showed that treatment with the drug for 24 weeks was generally safe and well tolerated, with a safety profile similar to that in patients aged 6 years and older, the company said.

The most common adverse event (≥30%) was cough (63%). Most adverse events were mild or moderate in severity. Four patients experienced serious adverse events (two pulmonary exacerbations, one case of gastroenteritis, one case of constipation). Three patients discontinued treatment owing to treatment-emergent adverse events or elevated enzyme levels on liver function tests.

"Research suggests Orkambi could impact CF outcomes in patients as young as 2 years old. This approval is a significant development that enables physicians to begin treating the underlying cause of the disease in this population earlier than ever before," John McNamara, MD, medical director of the CF program at Children's Minnesota and lead study researcher, said in a company news release.

Orkambi oral granules are available in two doses (lumacaftor 100 mg/ivacaftor 125 mg, and lumacaftor 150 mg/ivacaftor 188 mg) for weight-based dosing and should be available within 2 to 4 weeks, the company said.

CF affects about 30,000 people in the United States. The F508del mutation is the most common cause of CF. People with two copies of this mutation (one inherited from each parent) account for roughly half of the CF population in the United States.

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