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Cystic Fibrosis Drugs Licensed for Use in Younger Children

The Medicines and Healthcare products Regulatory Agency (MHRA) has extended the licence of the cystic fibrosis medicines Kaftrio (ivacaftor, tezacaftor, and elexacaftor) and Kalydeco (ivacaftor) for children aged 2-5 years old.

Kaftrio and Kalydeco, known as CFTR modulator therapies, are taken together by patients with cystic fibrosis as a long-term treatment to manage their symptoms.

Both medicines, manufactured by Vertex Pharmaceuticals, were already authorised for use in treating cystic fibrosis in older children and adults who had at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. 

The gene is responsible for a protein that supports the movement of chloride in and out of cells. Some mutations in the CFTR gene result in the CFTR proteins developing abnormally, leading to reduced chloride movement in the cells of those with cystic fibrosis. 

The active ingredients in these treatments — ivacaftor, tezacaftor, and elexacaftor — work by interacting with certain abnormal CFTR proteins, so they open more often to improve chloride movement in and out of cells.

Julian Beach, MHRA interim executive director, healthcare quality and access at the MHRA, said: "We have prioritised the assessment of Kaftrio and Kalydeco for this age range in view of the unmet needs of children with cystic fibrosis."

Positive Results From a Phase 3 Trial

The MHRA said its decision was supported by evidence from a 24-week, phase 3 clinical study involving 75 patients aged 2-5 years old with a confirmed diagnosis of cystic fibrosis and at least one F508del mutation. In the study, patients continued their usual therapies, such as bronchodilators or inhaled antibiotics, but came off any CFTR modulator therapies they may have been on, other than the study drugs.

Results showed that chloride concentrations in sweat reduced by 57.9 mmol/L over the course of the study and this effect was comparable to the effect on sweat chloride in older children and adults where clinical efficacy was demonstrated for this combination.

Treatment with Kaftrio and Kalydeco was found to be safe and well tolerated by patients, the MHRA said, with the most common side effects being a common cold, including sore throat and nasal congestion, headache, dizziness, diarrhoea, stomach pain, changes in the types of bacteria in the mucus, increased liver enzymes, and a rash. 

For children aged 2-5 years old and under 14 kg in weight, the recommended dose is a sachet of Kaftrio granules containing 60 mg ivacaftor, 40 mg tezacaftor, and 80 mg elexacaftor given in the morning, with a further sachet of Kalydeco granules with 59.5mg of ivacaftor taken in the evening, at least 12 hours apart.

For children weighing 14 kg or more, the recommended dose is a sachet of Kaftrio granules containing 75 mg ivacaftor, 50 mg tezacaftor, and 100 mg elexacaftor given in the morning, and a further sachet of Kalydeco granules with 75 mg of ivacaftor taken in the evening, at least 12 hours apart.

NICE Assessment of Therapies

The decision to extend the licence is separate from the ongoing appraisal process currently being conducted by the National Institute for Health and Care Excellence (NICE). Last week, the regulator published draft guidance stating that while three CFTR potentiators — Orkambi, Symkevi, and Kaftrio — were clinically effective treatments for patients with cystic fibrosis, they were too expensive to be recommended for NHS use in England.

The draft guidance is currently subject to a consultation, with a second evaluation committee meeting scheduled for 14 December.

Commenting on today's MHRA's decision, David Ramsden, chief executive of the Cystic Fibrosis Trust, said: "Today's news reinforces the need to ensure that the current NICE process rapidly results in a comprehensive deal to end the uncertainty for all who could benefit in the future."