FDA Approves Trikafta to Treat Children Starting at Age 6

The U.S. Food and Drug Administration (FDA) has approved expanding the use of Trikafta (elexacaftor, tezacaftor, and ivacaftor) to children with cystic fibrosis (CF), ages 6 and older, who have at least one F508del mutation in the CFTR gene or a CFTR mutation that responds to Trikafta in laboratory studies.

Use of the triple combination therapy, first approved in the U.S. in 2019, was previously limited to CF patients ages 12 and older with these mutations. According to Vertex Pharmaceuticals, Trikafta’s manufacturer, this label expansion will make the medication available to many more children in the U.S.

“Today’s approval is a critical milestone in our efforts to deliver medicines that help treat the underlying cause of this devastating disease as early in life as possible. We can now reach approximately 1,500 newly eligible children in the U.S.,” Reshma Kewalramani, MD, Vertex’s president and CEO, said in a press release.

Vertex applied for this label expansion last year, after data from the Phase 3 AURORA clinical trials (NCT03525444 and NCT03525548) indicated that Trikafta is safe in children as young as age 6.

Findings from another Phase 3 study (NCT03691779), which included 66 children ages 6 to 11 who had either two F508del mutations or one F508del and one minimal function mutation, were recently published.

Results showed that Trikafta treatment improved the children’s lung function and quality of life, with a safety profile comparable to that seen in older populations. Common side effects reported in the trial included cough, headache, and fever; these were usually mild or moderate in intensity.

“Clinical experience with Trikafta in patients 12 and older over the past 20 months has demonstrated this medicine has a meaningful and unprecedented clinical benefit for patients. I look forward to now being able to treat younger patients with this breakthrough medicine, including those who have not presented major signals of disease progression,” said Terri Laguna, MD, the associate director of the Cystic Fibrosis Center at Ann & Robert H. Lurie Children’s Hospital of Chicago.

CF is caused by mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene, resulting in the production of a malfunctioning CFTR protein. F508del is the most common CF-causing mutation, found in about 9 out of every 10 CF patients.

Trikafta is an oral combination of three CFTR modulators — medications that work to improve the functionality of the mutated CFTR protein — called elexacaftor, tezacaftor, and ivacaftor.

In line with this new approval, Vertex has made an additional dosage strength of Trikafta tablets available: elexacaftor at 50 mg, tezacaftor at 25 mg, and ivacaftor at 37.5 mg, combined with ivacaftor at 75 mg.

“In addition to bringing Trikafta to a younger patient population, patients not previously eligible for any CFTR modulator will now be able to access a treatment that targets the underlying cause of their disease,” Laguna said.

Outside the U.S., Trikafta is approved to CF patients with specific mutations ages 12 and up in Switzerland, Australia and Israel, as well as in the European Union and the U.K., where the therapy is marketed as Kaftrio.

Vertex has applied to the European Medicines Agency and the U.K.’s Medicines & Healthcare products Regulatory Agency seeking a similar expanded approval for children as young as 6. The company is also planning to file for this expanded use in Switzerland, Australia, and Israel this year.