Trikafta, with one month’s use, helps to clear thick mucus from lungs

Gains in nutrition, easing of respiratory symptoms also reported

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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One month of treatment with Trikafta, a triple combo of elexacaftor, tezacaftor, and ivacaftor, helped to clear mucus from the airways of adolescents and adults with cystic fibrosis (CF), a study found.

Mucus became less thick, which may have helped in preventing its buildup in the airways, increasing a patient’s risk of recurrent infections and lung damage.

Benefits in lung function, respiratory symptoms, and nutrition also were found.

The study, “Effect of elexacaftor/tezacaftor/ivacaftor on mucus and mucociliary clearance in cystic fibrosis,” was published in the Journal of Cystic Fibrosis.

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Trikafta is a triple-combination therapy for children, adults with cystic fibrosis

CF is caused by mutations in the gene coding for CFTR, a protein that acts like a gate or channel on the surface of cells, allowing chloride ions to move through. This movement helps control the thickness of mucus.

Thick mucus clogs the airways of patients, putting them at risk of a number of CF respiratory symptoms and chronic infections.

Vertex Pharmaceuticals’ Trikafta, marketed as Kaftrio in Europe, is a CFTR modulator given to treat CF in children and adults who have at least one copy of F508del — the most common CF-causing mutation — or other responsive mutation.

While considered effective at improving patients’ “lung function, exacerbation frequency, respiratory symptoms, and nutritional indices,” less is known about Trikafta’s effects on mucociliary clearance. This refers to the mechanism used by cilia (short, hair-like structures on a cell’s surface) to move mucus and microorganisms such as bacteria out of places like the airways to keep them clean.

A team of researchers in the U.S. enrolled 44 adolescents and adults with CF, ages 12 to 54, prior to starting on Trikafta. Just over half (52%) previously had been treated with Orkambi (lumacaftor/ivacaftor) or Symdeko (tezacaftor/ivacaftor).

Mucociliary clearance was measured at the study’s start, or baseline, and one month into treatment with Trikafta. The researchers also collected samples of sputum (phlegm) and exhaled breath condensate, or breath condensed via cooling.

‘Markedly’ quickly mucociliary clearance seen with Trikafta’s use

The rate of mucociliary clearance, measured over the course of one hour, increased significantly from baseline to one month, from an average 14.8% to 22.8%, indicating faster mucociliary clearance with Trikafta’s use.

An analysis of sputum samples found that the proportion of solid materials, or dry weight, had fallen significantly from an average 3.4% to 2.2%. A lower proportion of solid materials suggests that mucus is less thick.

Trikafta “improved the hydration of respiratory secretions (% solids) and markedly accelerated [mucociliary clearance],” the researchers wrote. No changes were observed in any of the parameters measured in exhaled breath condensate.

As in previous studies, Trikafta led to improvements in patients’ lung function, lower sweat chloride levels, and increases in body weight. Treatment also eased their respiratory symptoms.

“These data confirm the link between CFTR function, mucus solid content, and MCC [mucociliary clearance] and help to define the utility of MCC and mucus-related bioassays in future efforts to restore CFTR function in all people with CF,” the researchers concluded.

The study was supported in part by the CF Foundation.