Combination therapy involving three drugs—elexacaftor, tezacaftor, and ivacaftor—can achieve positive, lasting effects in patients with cystic fibrosis, according to research published in the European Respiratory Journal

Researchers from Charité – Universitätsmedizin Berlin and the Max Delbrück Center found this form of medication improves the symptoms of cystic fibrosis in many patients, making mucus in the airways less sticky and significantly reducing lung inflammation. 

Two years ago, a research group headed by Charité showed that combination therapy involving the three drugs was effective in a large portion of patients with cystic fibrosis, a hereditary disease, meaning that the treatment noticeably improved both lung function and quality of life. Now, the team headed by Marcus Mall, who has been the lead researcher in both studies, has investigated for the first time whether this form of treatment is also helpful in the long term, meaning over a period of 12 months or more. 

To examine this, the researchers took a closer look at the sputum, the secretions from patients’ respiratory tracts. “In patients with cystic fibrosis, the mucus in the airways is very sticky because it doesn’t contain enough water, and the mucins, the molecules that form mucus, adhere too much due to their chemical properties. This results in thick, sticky mucus, which clogs the airways, making it harder for patients to breathe and leading to chronic bacterial infection and inflammation of the lungs,” says Mall, director of the department of pediatric respiratory medicine, immunology, and critical care medicine and the Christiane Herzog Cystic Fibrosis Center at Charité, in a release.

In the current study, the researchers show that a combination of elexacaftor, tezacaftor, and ivacaftor results in less viscous respiratory secretions and decreasing inflammation and bacterial infection in the lungs of cystic fibrosis patients. “What’s more, the effects lasted over the entire one-year study period. This is really important because previous medications caused a rebound in the bacterial load in the airways,” says Dr Simon Gräber, who also works in the department of pediatric respiratory medicine, immunology, and critical care medicine at Charité and was one of the co-leaders of the study, in a release. Seventy-nine adolescents and adults with cystic fibrosis and chronic lung disease participated in the trial.

A Major Step in Treating Cystic Fibrosis

“This is a major step forward in treating cystic fibrosis,” Mall says in the release. “At the same time, it would be premature to say that patients have been normalized, let alone cured. Chronic lung changes arising over many years of living with the disease cannot be reversed, unfortunately.” This means patients with advanced lung disease will still need to rely on established treatments involving inhaling mucus-thinning medications, taking antibiotics, and physical therapy.

“We plan to forge ahead with our research on how to make treatments that address cystic fibrosis via the molecular defects that cause the disease—like the triple medication combination studied here—even more effective. This includes starting treatment in early childhood with the goal of preventing chronic lung changes wherever possible,” Mall notes in the release. 

Gräber adds, “Aside from that, this therapy is not available to about 10 percent of our patients right now due to their genetic conditions. That’s why we are also hard at work on research involving new molecular treatments so we can treat all people with cystic fibrosis effectively.”

The researchers are also working to advance their understanding of mucus defects in cystic fibrosis and develop new mucolytics, drugs that thin and loosen the mucus. This research could also benefit patients with common chronic inflammatory lung diseases such as asthma and COPD.

Photo caption: Combination therapy involving three drugs—elexacaftor, tezacaftor, and ivacaftor—makes the mucus in the airways of cystic fibrosis patients (shown in the figure above) less thick and sticky. This makes it easier for the lungs to clear bacteria, and there are fewer respiratory inflammation cells.

Photo credit:  Laura Schaupp