Trikafta Keeps Lung Function From Declining for 2 Years: Study

In study, mean difference in ppFEV1 between those on, not on Trikafta reached 16.91 percent points

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Trikafta (elexacaftor/tezacaftor/ivacaftor) was seen to keep lung function from getting worse in people with cystic fibrosis (CF) for up to two years, a study found.

These findings counter previous studies wherein the active ingredients in Trikafta, alone or in combinations of two, were seen to slow, but not halt, lung function decline.

The triple combination “is the first CFTR modulator therapy shown to halt lung function decline over an extended time period,” the researchers wrote.

The study, “Effect of elexacaftor/tezacaftor/ivacaftor on annual rate of lung function decline in people with cystic fibrosis,” was published as a short communication in the Journal of Cystic Fibrosis.

CF happens due to mutations in the CFTR gene, which provides instructions for making a protein of the same name. The mutations cause the CFTR protein to fold into a wrong shape or not be produced at all, resulting in mucus being too thick.

When this thick mucus builds up in the lungs, breathing can be difficult and the airways become inflamed.

Trikafta contains elexacaftor and tezacaftor, which help CFTR fold correctly, and ivacaftor — also marketed independently as Kalydeco — that binds to the protein and holds it open so more salt can pass through it. This combined action can make mucus less thick and help relieve the symptoms of CF.

The therapy is used to treat CF in people ages 6 and up who have at least one copy of the F508del mutation — the most common type of disease-causing mutation — or another responsive mutation in the CFTR gene.

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Trikafta’s effects on lung function in CF

Data from people treated for almost three years revealed Trikafta continues to be safe and brings benefits to lung function and breathing symptoms by helping the CFTR protein be more effective.

To know more about how Trikafta keeps lung function from declining over time, the researchers watched for changes in ppFEV1, which is the maximum amount of air a person can breathe out in a second.

The study included 468 people who took part in either of two Phase 3 clinical trials — the AURORA F/MF (NCT03525444) or the AURORA F/F (NCT03525548) — and who may have rolled over into an open-label 192-week extension (NCT03525574). Their mean age was 26.41.

To choose controls, the researchers used propensity score matching, a statistical method that matches each person in a group to one or more persons with similar characteristics in another group.

The matched controls were 1,714 people with a diagnosis of CF from the CF Foundation Patient Registry who had at least one copy of the F508del mutation yet weren’t eligible for CFTR modulator therapy. Their mean age was 25.77.

Those on Trikafta started off from baseline with a mean ppFEV1 value that was 61.05 percentage points of the value seen in the average healthy person. Controls had a mean baseline ppFEV1 value of 62.60 percentage points.

Being on Trikafta kept lung function from getting worse over time. Those on treatment saw their annualized rate of ppFEV1 increase a mean 0.39 percentage points, whereas controls saw it decrease a mean 1.92 percentage points. After two years, the mean difference in ppFEV1 between those on Trikafta and those who weren’t reached 16.91 percent points.

These observations held true regardless of the number of copies of the F508del mutation, one or two.

“On average, there was no lung function loss over the 2-year period,” the researchers wrote, noting their findings suggest “treatment [with Trikafta] has a significant impact on the progression and trajectory of CF lung disease.”

The study was funded by Vertex Pharmaceuticals, which has developed and sells Trikafta.

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