The Medicines and Healthcare products Regulatory Agency (MHRA) has today (15 November 2023) extended the use of cystic fibrosis medicines Kaftrio (ivacaftor, tezacaftor and elexacaftor) and Kalydeco (ivacaftor) for children aged two to five.
Image credit: Medicines and Healthcare products Regulatory Agency (MHRA)
These drugs were already approved for use in the treatment of cystic fibrosis with a common gene mutation in patients six years of age and older, and today’s announcement extends that approval.
We have prioritized evaluating Kaftrio and Kalydeco in this age range in view of the unmet needs of children with cystic fibrosis. As with all products, we will closely monitor the safety of Kaftrio and Kalydeco in this age range.”
Julian Beach, MHRA Interim Chief Executive, Quality and Access to Healthcare
Cystic fibrosis is an inherited condition that causes sticky mucus to build up in the lungs and digestive system. This causes lung infections and problems with digestion. Symptoms usually start in early childhood and vary from child to child, but the condition slowly worsens over time, with the lungs and digestive system becoming increasingly damaged. Over 10,600 people live with this condition in the UK.
Kaftrio and Kalydeco are taken together by patients as a long-term treatment to manage the symptoms of cystic fibrosis. They are used to treat the disease in patients with at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. F508del is the most common cystic fibrosis causing mutation.
This gene is responsible for a protein that supports the movement of chlorine in and out of our cells. Some mutations in the CFTR gene cause the CFTR proteins to develop 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 the movement of chloride in and out of cells.
The drugs, known as CFTR modulator treatments, are available as sachets of granules that are mixed with 5ml of soft food and consumed immediately, immediately before or after a fat-containing meal/snack.
For children aged two to five years weighing less than 14 kg, the recommended dose is one sachet of Kaftrio granules containing 60 mg ivacaftor, 40 mg tezacaftor and 80 mg elexacaftor given in the morning and one additional sachet of Kalydeco granules with 59.5 mg ivacaftor. in the evening, at least 12 hours apart.
For children aged two to five years who weigh 14 kg or more, the recommended dose is one sachet of Kaftrio granules containing 75 mg ivacaftor, 50 mg tezacaftor and 100 mg elexacaftor given in the morning and one additional sachet of Kalydeco granules containing 75 mg ivacaftor . taken in the evening, at least 12 hours apart.
The extension of the existing license to this age group is supported by data from studies of this drug combination in patients aged 12 years and older, in addition to data from a 24-week phase 3 clinical study in 75 patients aged two to five years, which had a confirmed diagnosis of cystic fibrosis and at least one F508del mutation.
In this study, patients continued their cystic fibrosis treatments, such as bronchodilators or inhaled antibiotics, but avoided any CFTR modulator therapy they might have been taking other than the study drugs.
In the study, safety was assessed by observing drug side effects, and treatment effect was assessed using change in sweat chloride concentrations.
The study showed that treatment with Kaftrio and Kalydeco was safe and well tolerated by patients, with a safety profile consistent with that seen in older age groups.
In this study of two- to five-year-old children, sweat chloride concentrations decreased 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 the clinic efficacy was demonstrated for this combination.
The most common side effects of the drug are a common cold, such as sore throat and nasal congestion, headache, dizziness, diarrhea, stomach pain, changes in the types of bacteria in the mucus, elevated liver enzymes, and rash.
As with any medicine, the MHRA will closely monitor the safety and effectiveness of both Kaftrio and Kalydeco. Anyone who suspects they are having a side effect from these medicines is encouraged to speak to their doctor, pharmacist or nurse and report it directly to the Yellow Card scheme, or via the website (https://yellowcard.mhra.gov.
