Trikafta Found Safe, Effective for Children Ages 6–11

Trikafta, a medication that combines three different therapies (elexacaftor/tezacaftor/ivacaftor), is safe and effective in children with cystic fibrosis (CF) ages 6 to 11 who have certain genetic mutations, results from a Phase 3 clinical trial show.

The U.S. Food and Drug Administration (FDA) recently accepted for review a supplemental new drug application for the use of Trikafta in children as young as 6. That decision is supported by the new Phase 3 findings. A final decision by the FDA is expected by June.

The study, “A Phase 3 open-label study of ELX/TEZ/IVA in children 6 through 11 years of age with CF and at least one F508del allele,” was published in the American Journal of Respiratory and Critical Care Medicine.

Trikafta, marketed by Vertex Pharmaceuticals, is approved for the treatment of CF in patients 12 and older who have at least one copy of the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene — the most common mutation causing CF.

However, the medication “has not been evaluated in children [younger than] 12 years of age,” researchers wrote.

Now, the safety and efficacy of Trikafta were evaluated in a Phase 3 study (NCT03691779) involving 66 children age 6 to 11 who have two F508del mutations or one F508del and one minimal function mutation.

The study had an open-label design, meaning all children received Trikafta for 24 weeks. Children weighing 30 kilograms (about 66 pounds) or more received the full adult daily dose — 200 mg elexacaftor, 100 mg tezacaftor, and 75 mg ivacaftor as a fixed-dose combination tablet in the morning, and 75 mg ivacaftor as a monotherapy tablet in the evening — while children weighing less than 30 kg received half of that dose.

The safety data were consistent with those observed in previous studies with older patients, and the medication was generally well-tolerated.

“The most common reported adverse events (AEs) included cough, headache, and pyrexia [fever]; in most of the children who had AEs, these were mild or moderate in severity,” the researchers wrote.

Significant improvements in clinically relevant parameters were observed with Trikafta treatment, including a 10.2 percentage point improvement in the percent predicted forced expiratory volume in one second (ppFEV1, a measure of lung function), a seven point increase in the Cystic Fibrosis Questionnaire–Revised respiratory domain score (a tool that measures the impact of CF on overall health, daily life, perceived well-being, and symptoms), and an almost two point reduction in the lung clearance index (a measure of lung ventilation) compared with the pre-treatment values.

Trikafta treatment also reduced the levels of chloride in sweat (the gold standard in diagnosing CF).

“We saw greater improvements in sweat chloride than those previously seen in adults and adolescents,” Susanna McColley, MD, from Ann & Robert H. Lurie Children’s Hospital of Chicago, study’s senior author, said in a press release. “This strong response to treatment may lead to better long-term clinical outcomes of cystic fibrosis.”

Treatment with Trikafta for 24 weeks also resulted in significant improvements in nutritional status, as measured by body mass index-for-age z-score, compared to pre-treatment. Of note, a better nutritional status in CF patients is associated with a better lung function and survival rate.

“The most exciting aspect of our findings is that this population of children had normal lung function at the start of the study and still had a significant improvement,” McColley said. “Coupled with what we saw in studies and in practice with the older population, starting treatment earlier may avert serious long-term complications and really change the trajectory of health for children with cystic fibrosis.”

The findings showed Trikafta to be safe and efficacious in children with CF aged 6 to 11 who have at least one copy of the F508del mutation, thus “supporting its use in this patient population,” the researchers concluded.

McColley noted that “people with cystic fibrosis who are demographically characterized as having a race other than white or ethnicity characterized as Hispanic are less likely to have an F508del mutation. This is important because as with other acute and chronic conditions, these populations have more severe disease and lower life expectancy. As drug development continues, we are focused on having a highly effective treatment or cure for everyone with cystic fibrosis.”