"Breakthrough", "milestone" - the professional world rarely reacts so euphorically to a new therapy as it does to this: An international team of doctors led by Peter Middleton from the University of Sydney has presented a combination of three active ingredients for cystic fibrosis in the journal "NEJM". The treatment significantly improves the situation in up to 90 percent of patients with metabolic disease. In the US, Trikafta was approved on 21 October for patients 12 years of age or older, following an accelerated procedure. The European authority EMA already has an application for approval.
Most common congenital metabolic disease in Europe
Cystic fibrosis is the most common congenital metabolic disease in Europe. According to the Helmholtz Center Munich, around 200 children are born with the disease each year in Germany.
In the disease, defective chloride channels on the surface of cells cause phlegm to become so viscous in the bronchi, pancreas, sweat glands, digestive tract, and other organs that it does not drain properly. Consequences of the life-threatening and so far incurable illness are for example permanent cough, chronic diarrhea and recurrent pneumonia.
The disease is caused by mutations in the CFTR gene. More than 1700 such changes can cause cystic fibrosis - also called cystic fibrosis (CF). The new therapy targets by far the most common mutation: Phe508del. Although various therapies have been approved in recent years, they are only suitable for smaller subgroups of patients.
"In Europe, about 80 to 90 percent of patients have this most common mutation," says Sabine Renner, who heads the Outpatient Clinic for Cystic Fibrosis at the Medical University of Vienna.
More than one hundred centers in 13 countries and more than 400 patients, ages 12 and up, took part in the study that was published with the Phe508del mutation. Renner and her colleagues also looked after study participants.
Half of the subjects received the three active substances Elexacaftor, Tezacaftor and Ivacaftor, the others received a sham preparation. After four weeks, lung function was improved by about 14 percent compared to placebo, and the rate of pulmonary impairment was 63 percent lower.
"Fitter already after two weeks"
"Already after two weeks, the patients under the therapy are better, respiratory improved and show the enormous improvement in lung function," says Sabine Renner. "In addition, it shows a completely uncomplicated weight gain, even in patients who have always had to 'fight for every gram'."
Two of the 200 patients treated with the drug discontinued treatment - due to hypertension and rash. Overall, 28 patients treated with the combination had serious side effects compared to 42 in the equally large placebo group. These side effects included an exacerbation of lung problems - more frequent in participants in the placebo group than in those receiving the drug combination. In general, the authors speak of an acceptable side effect profile.
Who paid for it?
The study was funded, among others, by the manufacturer of the product, Supported by Vertex Pharmaceuticals.
The drug Trikafta was approved in the US for patients over 12 years with the corresponding mutation in the CFTR gene. The FDA says that the threefold drug in the second, unpublished study improved lung function by 10 percent compared to the current two-drug combination.
For the first time a causal therapy is available for the majority of patients, says Mirjam Stahl from the German Center for Lung Research (DZL) in Heidelberg. "In my view, it is absolutely appropriate to speak in superlatives of this therapy." She speaks of significant improvements that would reflect better physical performance and better life expectancy for patients.
Do not forget the other patients
Renner emphasizes that one should not forget those concerned who would not be eligible for the therapy: "Patients with other mutations, with incompatibility of the triple therapy, with a significant liver disease - which is quite common in CF, patients who have a pregnancy plan or pregnant, and patients in whom interactions with other medicines are a contraindication. "
Similarly, Francis Collins of the National Institutes of Health in Bethesda (US state of Maryland) commented in a commentary in "NEJM." The development of the new therapy was supposed to be "a reason for a big celebration" because in the future 90 percent of the patients could be treated safely and effectively. But one should not give up the other patients. The goal of the research is a permanent cure that works for all concerned.
