Thursday August 11, 2022 – Author:
ham
A promising drug combination has been available to patients with cystic fibrosis for two years. The triple therapy was previously reserved for children under the age of twelve. Fortunately, a study with Charité participation has changed this.
The treatment of incurable cystic fibrosis has made progress. With the so-called CFTR-Modulatoren drugs are available for the first time that target the cause of the disease – a defect in an ion channel. In almost 90 percent of those affected, the defect is triggered by a specific error in the CFTR gene. This is where the new active ingredients come into play.
A combination of three CFTR modulators (elexacaftor/tezacaftor/ivacaftor) has been available in Europe since August 2020, which can increase the function of the ion channel to around 50 percent of the normal value in patients with one copy of this mutation, thus improving their lung function and quality of life improved. Until the beginning of the year, however, the combination of active ingredients was only approved for children over the age of twelve.
Study in children led to approval in Europe
The promising drug cocktail was tested on younger children as part of a strictly controlled clinical study. The results finally led to approval from 6 years of age in 2022. The Charité was one of the 34 study centers worldwide and co-managed it. The results have now been published in the American Journal of Respiratory and Critical Care Medicine.
After that, the functionality of the CFTR ion channel increased significantly in the 6- to 11-year-old study participants and the lung function and quality of life of the children improved. Overall, the therapy showed a good safety profile and was well tolerated by the children. The side effects corresponded to those that had already been observed in older patients.
Measurable effects after half a year
“I was surprised and very pleased to see that the children noticed a positive effect despite the early stage of the disease and the short duration of treatment,” says first author Prof. Dr. Marcus Mall. “These results have contributed to the European Medicines Agency approving the triple therapy for children aged 6 and over earlier this year, so that we can already use it from this age. I expect that the earlier treatment of the basic defect that is now possible will improve the health of patients with cystic fibrosis significantly improved over the long term.”
121 children between the ages of 6 and 11 who had a corresponding mutation in their genome took part in the randomized placebo-controlled study. Every second child received the combination of active ingredients for six months, the others received a placebo. Unfortunately, this type of clinical study is far too rare in the development of drugs for children, says Einstein Professor Mall. “Often no control groups are examined in children, but conclusions are drawn from studies with adults on the effects in children. However, children are not small adults, so high-quality studies are very important for the development of safe and effective medicines.”
Toddlers and infants are also said to benefit
The research team is currently investigating the safety and effectiveness of triple therapy in children between the ages of two and five. But it shouldn’t stay that way – infants will also soon be treated with it, as Mall suggests: Since cystic fibrosis can now be diagnosed as part of newborn screening within the first few weeks of life, people with cystic fibrosis can now be treated causally as early as newborns “and so hopefully themselves prevent early damage to the lungs and possibly other affected organs such as the pancreas. We are slowly approaching this age.”