Trikafta safe, effective for treating CF in analysis of clinical trials

Researchers compared therapy against 2 other CFTR modulators, placebo

Steve Bryson, PhD avatar

by Steve Bryson, PhD |

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A pooled analysis of data from multiple clinical trials of more than 1,100 people with cystic fibrosis (CF) confirms Trikafta effectively improves lung function, sweat chloride levels, and health-related quality of life.

“Further monitoring and assessment of the safety profile of [Trikafta] are necessary to ensure its long-term efficacy and safety in CF patients,” the researchers wrote.

The results of the pooled analysis was published in SAGE Open Medicine in the study “Elexacaftor–tezacaftor–ivacaftor for cystic fibrosis with Phe508del mutation: Evidence from randomized controlled trials.”

A CFTR modulator, a type of therapy that helps correct specific defects in the CFTR protein, the underlying cause of CF, Trikafta is a combination of three oral medications: elexacaftor, tezacaftor, and ivacaftor. It’s approved for patients ages 2 and older with at least one F508del mutation, the most common CF-causing genetic defect.

Individual clinical trials have demonstrated that Trikafta outperformed existing therapies with respect to improving lung and CFTR protein function, along with quality of life.

Here, researchers in China pooled the results of multiple published trials, called a meta-analysis, to evaluate the effectiveness and safety of Trikafta across a large group of people with CF. They selected six trials that randomly assigned participants to either Trikafta, a placebo, or the CFTR modulators Kalydeco (ivacaftor) or Symdeko (tezacaftor, ivacaftor).

The trials included 563 males and 562 females, with an average age of 27.7. Trikafta was assigned to 576 patients. The remaining 549 received either a placebo, Kalydeco, or Symdeko.

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How Trikafta stacks up

Lung function was assessed by the amount of air that can be quickly exhaled in one second after a deep breath, a test called ppFEV1. Other measures included sweat chloride levels, a marker of CFTR function, and the CF questionnaire-revised respiratory domain (CFQ-R RD), a patient-reported assessment of lung function.

Across all patients, the analysis revealed Trikafta markedly improved ppFEV1 values by 10.29% over the placebo/Kalydeco/Symdeko group. In a subgroup analysis of patients with at least one F508del mutation, the triple combination therapy significantly outperformed the placebo by 13.44% ppFEV1 and the Kalydeco/Symdeko group by 8.33%

Health-related quality of life, as assessed by CFQ-R RD scores, significantly improved by 14.59 points with Trikafta versus a placebo, Kalydeco, or Symdeko. Consistent with the efficacy analysis, Trikafta significantly outperformed the placebo by 15.23 points in patients with at least one F508del mutation and by 14.12 points among those with two mutations.

Trikafta also reduced sweat chloride concentrations by 40.30 millimoles/L (mmol/L), a sign of increased CFTR function, over the placebo/Kalydeco/Symdeko group. Among those with at least one F508del mutation, Trikafta reduced sweat chloride by 44.12 mmol/L and by 38.12 mmol/L in those with two mutations.

Although the incidence of adverse events (AEs) was higher with Trikafta than a placebo, Kalydeco, or Symdeko, the difference wasn’t statistically significant. The rate of serious AEs was significantly lower in the Trikafta group than in the other groups.

There were no differences in the incidence of AEs leading to treatment discontinuation across all the groups and no differences in serious AEs between Trikafta and a placebo. There were statistically significant differences in mild and moderate AEs in the Trikafta group over the other groups, but no differences in serious AEs. No deaths were reported.

Common AEs included pain in the throat, cough, common cold, headache, increased sputum, upper respiratory tract infection, and lung exacerbations, a sudden worsening of symptoms caused by infection.

“The findings from this study suggest that [Trikafta] is an effective treatment for CF patients,” the researchers said. “It shows significant improvements in lung function (ppFEV1), health-related quality of life (CFQ-R RD), and CFTR function (sweat chloride concentrations).”