#NACFC2021 – Trikafta Aids Patients Who Cannot Use Other Modulators

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Treatment with Trikafta improves lung function in people with cystic fibrosis (CF) who are not eligible for treatment with other CFTR modulators, according to interim data from an observational study.

Results were shared at this year’s North American Cystic Fibrosis Conference (NACFC) in the presentation, “Real-world clinical effectiveness of elexacaftor/tezacaftor/ivacaftor and ivacaftor in people with CF: Interim results from the HELIO study.” The study was supported by Vertex Pharmaceuticals, which markets Trikafta.

CF is caused by mutations that lead to defects in the CFTR protein, which helps to control the movement of water in and out of cells. CFTR modulators are a class of medication that work to correct the underlying defect in this protein in people with specific CF-causing mutations.

Trikafta (marketed as Kaftrio in Europe) is an oral combination therapy containing three CFTR modulators: elexacaftor, tezacaftor, and ivacaftor. The medication was first approved in the U.S. in 2019; that approval has since been expanded to include more mutations and patients as young as 6 years old.

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CF combination therapies | Cystic Fibrosis News Today | illustration of oral treatments

Trikafta Helps Lung Function in CF Patients With Certain Mutations

The new data come from HELIO, an observational U.S.-based study that is tracking outcomes in a specific set of CF patients, ages 12 and up, who are starting on Trikafta as a first treatment. Specifically, it includes patients who were not eligible for a CFTR modulator prior to Trikafta’s approval.

“The HELIO study was initiated in 2019, right after the [U.S.] approval, in order to evaluate the clinical effectiveness [of Trikafta] in a real-world setting” of patients 12 and older who were not previously eligible for other CFTR modulators, Vaidyanathan Ganapathy, PhD, director of real world evidence at Vertex, said at the NACFC.

This interim analysis included data for 100 patients who had been on Trikafta for at least six months. Just over half were male with a mean age of about 25, and the group had a mean follow-up time of 11.2 months. All had one F508del mutation (the most common CF-causing mutation), and either one minimal function mutation or an uncharacterized mutation.

Lung function was assessed with forced expiratory volume one (FEV1), a measure of how much air a person can blow out in one second. At the study’s start, the mean FEV1 score was about 71% of what would be predicted for a healthy person.

At six months after starting on Trikafta, the mean FEV1 score had increased significantly, by 10.4%. A similar change (9.5%) was seen through the end of the time patients were on the medication.

These changes indicate “a positive impact [of treatment] on lung function, and a clinically meaningful change” from before starting the treatment, Ganapathy said.

Trikafta’s use also led to a significant increase in body mass index (BMI), by a mean of 1.08 kilograms per square meter (kg/m2) at six months, and 0.96 kg/m2 through the latest time point measured.

BMI is a measure of body weight relative to height. Since people with CF often have digestive problems that makes it hard for them to get enough nutrients, it is common for patients to be underweight (i.e., have a low BMI), so increasing BMI indicates that the treatment is making it easier for patients to meet nutritional goals.

The treatment also substantially reduced the frequency of pulmonary exacerbations — times when lung symptoms suddenly worsen. In the year prior to starting on Trikafta, patients averaged 1.24 exacerbations per year. After starting on treatment, the rate was 0.49 exacerbations per year, representing a 61% reduction.

Among patients who had not been eligible for prior CFTR modulator therapies, treatment with Trikafta led to “clinically meaningful improvements in lung function, nutritional status, and pulmonary exacerbation rates,” Ganapathy concluded. These real-world findings are, overall, similar to the benefits seen in clinical trials of the medication, he added.

A study limitation is its observational design, which makes it difficult to draw reliable cause-and-effect conclusions, Ganapathy said. He also noted that the study was conducted during the COVID-19 pandemic, which may have affected outcomes.

“Once we have the final dataset, we’ll be doing more testing for the confounding [effects] of the pandemic,” he said.

Editor’s note: The Cystic Fibrosis News Today team is providing coverage of the virtual 2021 North American Cystic Fibrosis Conference (NACFC) Nov. 2–5. Go here to see the latest stories from the conference.