CF treatment Alyftrek shows lung benefits, per new data
Vertex says treatment may lower flare incidence, reduce antibiotic need
Vertex Pharmaceuticals presented new data highlighting additional clinical benefits and improved outcomes in people with cystic fibrosis (CF) treated with the triple combination Alyftrek (vanzacaftor/tezacaftor/deutivacaftor) or other CFTR modulators.
The data also suggest that Alyftrek may lead to fewer pulmonary exacerbations (flare-ups) and less antibiotic usage than Trikafta (elexacaftor/tezacaftor/ivacaftor), another of the Vertex’s CFTR modulators, according to a company press release. Trikafta is sold as Kaftrio in the European Union.
The findings were shared across multiple abstracts presented by the company at the North American Cystic Fibrosis Conference (NACFC), held Oct. 22-25 in Seattle.
CF is caused by mutations in the CFTR gene, which provides instructions for making a protein that regulates the movement of salt and water into and out of cells. When this protein is missing or doesn’t function properly, thick and sticky mucus builds up in the lungs and other organs, leading to most CF symptoms, including excessively high levels of chloride (a component of table salt) in sweat.
CFTR modulators are a class of therapies designed to bind to defective CFTR proteins and improve their function. By restoring the salt and water balance, they help the body produce thinner mucus, ease symptoms, and slow disease progression.
Sweat chloride studies
Trikafta is approved to treat people with CF, ages 2 or older, who carry at least one copy of a mutation that’s responsive to the therapy, including the most common CF-causing mutation, F508del.
Alyftrek, a next-generation triple combination approved in the U.S. and other regions for in patients 6 and older, was developed to provide better efficacy and more convenient once-daily dosing than Trikafta, which is taken twice daily. The new therapy combines tezacaftor, one of the modulators found in Trikafta, with two new modulators called vanzacaftor (VX-121) and deutivacaftor (VX-561).
Its approval was based on data from three Phase 3 clinical trials: the SKYLINE 103 (NCT05076149) and SKYLINE 102 (NCT05033080) studies, which enrolled CF patients 12 and older, and an ongoing study (NCT05422222) in younger children.
Results from the trials in older patients showed that Alyftrek reduced chloride levels in sweat more than Trikafta, suggesting a greater improvement in CFTR function. Both therapies led to similar stabilization of lung function and had comparable safety profiles.
At the NACFC, Vertex presented additional analyses from the SKYLINE 102 and SKYLINE 103 studies, reinforcing these findings and showing that greater reductions in sweat chloride levels were associated with fewer pulmonary exacerbations — including those requiring hospitalization or intravenous (into-the-vein, or IV) antibiotic treatment — and lower overall IV antibiotic use compared with participants on Trikafta who had a similar genetic makeup.
In a separate pooled analysis of more than 2,000 people with CF ages 12 and older who took part in Phase 3 trials of CFTR modulators — including Alyftrek — achieving chloride levels in sweat within or below the normal range after treatment was associated with reduced frequency of both IV and oral antibiotic use compared with those whose chloride levels remained higher.
Additional pooled data from Phase 3 and open-label extension studies, including participants treated with Alyftrek, also showed that patients who began CFTR modulator therapy at younger ages achieved greater CFTR function. Among children who were aged 6-11 when starting treatment, those who achieved lower sweat chloride levels experienced broader clinical benefits, including greater gains in lung function, easing of respiratory symptoms, improved nutritional status, and lower annual rates of pulmonary exacerbations.
Vertex also presented new real-world and long-term data on treatment with Trikafta. Other abstracts focused on the clinical characteristics and unmet needs of people with CF whose genetic makeup precludes response to current CFTR modulators.
About the Author
