Triple therapy shows promise for long-term treatment of cystic fibrosis

Airway mucus is less sticky and inflammation in the lungs is greatly reduced. The 3-in-1 combination provides sustained and sustained benefit in patients with cystic fibrosis (CF). Researchers from the Berlin Charité University and the Max Delbrück Center recently published their findings as European Respiratory Journal. According to their research, this form of the drug improves symptoms of CF in many patients.

Two years ago, a group of researchers led by Charité showed that a combination of three drugs, elexacaftor, tezacaftor and ivacaftor, helped most people with the genetic disease cystic fibrosis. . This means that this treatment significantly improves both pulmonary functions. and quality of life. Now, a team led by Professor Marcus Mohr, the principal investigator of both studies, is the first to investigate whether this form of treatment can also help long-term, for periods longer than 12 months. To find out, the researchers probed sputum, a secretion from the patient’s airways. “The mucus in the airways of people with cystic fibrosis is very thick because it doesn’t contain enough water and because of its chemical properties, the mucus-forming molecule, mucin, is attached to excess. The result is a thick mucus that can clog airways, make it difficult for patients to breathe, and lead to chronic bacterial infections and lung inflammation,” says Pediatric Respiratory, Immunology. explains Mohr, director of the School of Medicine, Department of Critical Care Medicine and the Christiane Herzog Center for Cystic Fibrosis. Charité.

In the current study, the researchers showed that the combination of elexacaftor, tezacaftor and ivacaftor resulted in less viscous respiratory secretions and reduced lung inflammation and bacterial infection in patients with cystic fibrosis. “Furthermore, the effect was sustained over the entire one-year study period, which is very important as previous medications caused a rebound in airway bacterial load,” says Simon, who also works in Pediatric Respiratory Medicine. Dr. Graeber explains. At Charité, he is responsible for medicine, immunology, and critical care, and was one of the co-leaders of the study. Seventy-nine adolescents and adults with cystic fibrosis and chronic lung disease participated in the trial.

Major step in treating cystic fibrosis, further research critical

“This is a big step forward in treating cystic fibrosis,” Moll said. “At the same time, it would be premature to say that the patient has normalized rather than cured. Unfortunately, living with the disease for many years has resulted in chronic lung changes that are unfortunately irreversible.” This means that patients with advanced lung disease must rely on established treatments such as inhaled mucus-thinning drugs, taking antibiotics, and physical therapy.

“We plan to explore ways to make therapies that address cystic fibrosis more effective, such as the triple therapy studied here, through the molecular defects that cause the disease. This includes starting treatment in early childhood with the goal of “preventing as many chronic lung changes as possible,” Mohr said. “Apart from that, about 10 percent of patients currently have no access to this treatment because of genetic disorders,” Graeber added. “That is why we are also passionate about researching new molecular therapeutics that can effectively treat all people with cystic fibrosis.”

Researchers are also working to advance our understanding of mucus defects in cystic fibrosis and to develop new mucolytic agents that thin and loosen mucus. This research may also benefit patients with common chronic inflammatory lung diseases such as asthma and COPD.

cystic fibrosis

Cystic fibrosis is one of the most common fatal genetic diseases worldwide. As many as 8,000 children, adolescents and adults are currently living with the disease in Germany. Due to an imbalance in the transport of salt and water across mucosal surfaces of the body, people with cystic fibrosis produce thick secretions that harm organs such as the lungs, intestines, and pancreas. This results in progressive deterioration of lung function and shortness of breath, and despite advances in treatment, it still significantly reduces life expectancy. Approximately 150-200 children are born with this rare disease in Germany each year.

About tripartite therapy

A three-drug combination of elexacaftor, tezacaftor and ivacaftor became available in Europe in August 2020. This therapy significantly improves lung function and quality of life in patients with her F508del, the most common genetic defect involved in CF. This means the treatment is an option for nearly 90 percent of people with cystic fibrosis. This combination therapy was approved in early 2022 for children aged 6 and older.