Introduction

The fixed-dose combination of lumacaftor / ivacaftor (trade name: Orkambi) has been approved in Germany since February 2018 for the treatment of cystic fibrosis in children between the ages of 6 and 11. As of January 2019, it can now also be given to children between the ages of 2 and 5. This medication is an option if there's a certain mutation (F508del) in a gene known as the CFTR (cystic fibrosis transmembrane conductance regulator) gene.

Cystic fibrosis is a genetic metabolic disease. It is caused by a defect in a gene called the CFTR (cystic fibrosis transmembrane conductance regulator) gene. This regulator influences the balance of salt and water in the mucus-producing gland cells, for example in the pancreas, bronchi and small intestine. The defect makes the mucus very thick and sticky. In the lungs, this thick mucus can’t be coughed up, which makes it hard to breathe and may cause a chronic cough. Bacteria can also collect in the mucus, repeatedly causing respiratory infections. Thick and sticky digestive juices damage the pancreas and reduce the body’s absorption of important nutrients in the bowel, increasing the risk of malnutrition and being underweight. The symptoms of cystic fibrosis already appear in children.

There is no cure for cystic fibrosis. The fixed-dose combination of lumacaftor / ivacaftor aims to improve the function of the CFTR, so that the mucus becomes less thick and sticky, and the symptoms improve.

Application

Lumacaftor / ivacaftor is available as tablets and granules, each at two doses:

  • Granules with 100 mg lumacaftor / 125 mg ivacaftor or with 150 mg lumacaftor / 188 mg ivacaftor
  • Tablets with 100 mg lumacaftor / 125 mg ivacaftor or with 200 mg lumacaftor / 125 mg ivacaftor

Children between 2 and 5 years of age

Children between 2 and 5 years of age take lumacaftor / ivacaftor in the form of granules every 12 hours before or after eating food containing fat. The fat helps the body to absorb the active ingredients better. The granules are mixed into a small amount of food, such as mashed fruit, fruit yogurt or milk. The food must be kept at room temperature or lower in order to not destroy the active ingredient.

The recommended dose will depend on the child's body weight. For children who weigh less than 14 kilograms (about 30 pounds), a single dose is 1 sachet of granules with 100 mg lumacaftor / 125 mg ivacaftor. For children who weigh 14 kilograms or more, a single dose is 1 sachet of granules containing 150 mg lumacaftor / 188 mg ivacaftor.

Children between 6 and 11 years of age

Children between 6 and 11 years of age take lumacaftor / ivacaftor as a tablet every 12 hours before or after eating food containing fat. The recommended single dose is 2 tablets with 100 mg lumacaftor / 125 mg ivacaftor. Tablets are swallowed whole (not chewed).

Other treatments

Children who have cystic fibrosis and the F508del mutation are given the best possible supportive (adjuvant) care. Supportive care should be tailored to the patient’s individual needs. It aims to relieve symptoms such as breathing difficulties as well as improve quality of life. It may include antibiotics for lung infections, mucus-thinning medications, physiotherapy and changes to their diet.

Assessment

Children between 2 and 5 years of age

In 2019, the Institute for Quality and Efficiency in Health Care (IQWiG, Germany) looked into whether the fixed-dose combination lumacaftor / ivacaftor has any advantages or disadvantages compared to best supportive care in children between 2 and 5 years of age who have cystic fibrosis and the F508del mutation.

But the manufacturer didn’t provide any suitable data with which to do the assessment.

Children between 6 and 11 years of age

In 2018, IQWiG looked into whether the fixed-dose combination lumacaftor / ivacaftor has any advantages or disadvantages compared to best supportive care in children between 6 and 11 years of age who have cystic fibrosis and the F508del mutation.

To answer this question, the manufacturer provided one study involving 204 children in that age range. 103 children were treated with the fixed-dose combination lumacaftor / ivacaftor, and 101 children were given a placebo (fake medication). All of the children also received symptom-reducing treatment. The treatment lasted 24 weeks. The results showed that the additional use of lumacaftor / ivacaftor had no benefits or drawbacks.

No difference

  • Life expectancy: None of the children died during the study.
  • Treatment stopped due to side effects: In each group, about 2 to 3 out of 100 children stopped their treatment due to side effects.
  • There were also no differences between the two groups in terms of:
    • Lung diseases getting worse
    • Difficulty breathing
    • Gastrointestinal (stomach and bowel) problems
    • Health-related quality of life
    • Serious side effects

More information

This information summarizes the main results of reviews produced by the Institute for Quality and Efficiency in Health Care (IQWiG, Germany). The reviews were commissioned by the German Federal Joint Committee (G-BA) as part of the “early benefit assessment of medications.” On the basis of these reviews and the hearings received, the G-BA passed a resolution on the added benefit of lumacaftor / ivacaftor (Orkambi) for children between between 6 and 11 years of age as well as children between 2 and 5 years of age.