CF treatment Alyftrek tops Trikafta for boosting life quality: Analysis
Study analyzes quality-of-life scores from 3 clinical trials
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Treatment with Alyftrek, a combination of vanzacaftor, tezacaftor, and deutivacaftor, led to better patient-reported health-related quality of life for children, adolescents, and adults with cystic fibrosis (CF), a study found.
The benefits were greater than those achieved with Trikafta (elexacaftor/tezacaftor/ivacaftor), according to a post-hoc analysis of three Phase 3 trials. A post-hoc analysis is typically an examination conducted after a study is completed and the findings are available.
“These findings suggest the potential for [Alyftrek] treatment to provide broad clinical benefits and highlight the possibility of increased [health-related quality of life] with greater CFTR function restoration,” the researchers wrote.
The study, “Improvements in health-related quality of life in people with cystic fibrosis ≥6 years of age treated with vanzacaftor/tezacaftor/deutivacaftor,” was published in the Journal of Cystic Fibrosis. It was funded by Vertex Pharmaceuticals, which sells both Alyftrek and Trikafta.
A new combination
CF is caused by mutations in the CFTR gene that result in the loss or dysfunction of the CFTR protein. This leads to the production of thick, sticky mucus that accumulates in the lungs, digestive system, and other organs, ultimately driving most of the disease’s symptoms.
Alyftrek comprises a new combination of three CFTR modulators, a class of medications that can boost the function of the CFTR protein in patients carrying specific disease-causing mutations.
Data from two Phase 3 clinical trials — SKYLINE 103 (NCT05076149) and SKYLINE 102 (NCT05033080) — enrolling adolescents and adults with CF demonstrated that Alyftrek had a more potent effect on CFTR function than Trikafta, while allowing more convenient dosing. Alyftrek, a next-generation, triple-combination CFTR modulator therapy approved in the U.S. in late 2024, is taken once daily, whereas Trikafta requires twice-daily administration.
Alyftrek was also as effective as Trikafta, an older triple-combination therapy, in measures of lung function in SKYLINE studies and in the Phase 3 RIDGELINE 105 trial (NCT05422222), which is testing Alyftrek’s safety and efficacy in children with CF ages 1 to 11.
The study team, which included researchers from Vertex, assessed changes in health-related quality of life with Alyftrek treatment by analyzing data from the three Phase 3 trials.
Analyzing scores
The researchers analyzed data from 926 participants in the SKYLINE trials using the CF Questionnaire-Revised-8 Dimensions (CFQ-R-8D) utility score. This score assesses CF-specific health-related quality of life for people with CF ages 14 and older, with higher scores indicating a better quality of life. The domains that are analyzed include respiratory issues, physical functioning, emotional functioning, vitality, digestive trouble (abdominal pain), body image, and whether CF affects the patient at school, work, or in daily activities.
SKYLINE 102 enrolled adolescents and adults with one CFTR gene copy having the F508del mutation, the most common CF-causing genetic change, and the other copy having a minimal function mutation — a mutation in which the resulting CFTR protein works minimally — known as an F/MF genotype. SKYLINE 103 enrolled participants with two copies of the F508del mutation, one copy combined with other mutations, or a set of other genetic makeups that respond to Trikafta treatment.
Overall, patients treated with Alyftrek showed significantly greater increases in CFQ-R-8D scores over 52 weeks (one year) compared with those taking Trikafta, especially when analyzing pooled data from both SKYLINE studies and data from SKYLINE 102 alone. In the pooled data, all nine CFQ-R-8D domains were more favorable to patients taking Alyftrek. The largest changes were seen in adolescents and adults with the F/MF genetic makeup.
The increase in health-related quality of life was 37.6% greater with Alyftrek than with placebo, after accounting for lung function, compared with Trikafta.
Analysis of 78 children from the RIDGELINE trial, ages 6 to 11, used the Cystic Fibrosis Questionnaire-Revised across non-respiratory domains. Improvements over Trikafta were observed across most domains through 24 weeks (about six months). The increases ranged from 3.7 points in emotional functioning to 7.2 points in social functioning.
“Given the once-daily dosing regimen of [Alyftrek], it was particularly noteworthy that a higher proportion of children taking [Alyftrek] (56 %) reported never stopping fun activities for their treatment at Week 24 compared to the [Trikafta] baseline (47 %) and a higher proportion of children (68 %) reported not feeling worried compared to the [Trikafta] baseline (55 %),” the scientists wrote. Baseline was defined as the day before the first Alyftrek dose following a four-week period in which children received Trikafta.
“In this study we show that [Alyftrek] treatment in children, adolescents, and adults led to improvements in measures of patient-reported [health-related quality of life] beyond what was achieved with [Trikafta],” the researchers concluded.
