Fixed-dose combination of lumacaftor / ivacaftor (Orkambi) for the treatment of cystic fibrosis in children

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).

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.

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

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.