FDA to Review Trikafta for Patients as Young as 6

The U.S. Food and Drug Administration (FDA) has accepted for review an application to expand the use of Trikafta as a treatment in children with cystic fibrosis (CF) ages 6 to 11 with at least one F508del mutation in the CFTR gene (the gene defective in CF) or a CFTR mutation that is responsive to the therapy.

The supplemental new drug application was submitted last year by Vertex Pharmaceuticals, Trikafta’s developer, after the Phase 3 AURORA clinical trials (NCT03525444 and NCT03525548) found Trikafta to be safe in children as young as 6.

The FDA has granted priority review to the supplemental application and assigned a Prescription Drug User Fee Act target action date of June 8,  meaning a decision is expected by that date.

“If approved for this expanded use, we will have the opportunity to treat the underlying cause of the disease earlier in life with Trikafta and potentially benefit approximately 1,500 additional children with CF,” Carmen Bozic, MD, executive vice president and chief medical officer of Vertex, said in a press release.

CF is caused by mutations in the CFTR gene, resulting in a malfunctioning CFTR protein that causes a buildup of thick mucus in the body’s tissues and organs. Trikafta is an oral combination of three CF therapies — elexacaftor, tezacaftor, and ivacaftor — that enhances CFTR protein function.

The therapy is effective in individuals who have at least one copy of the CFTR gene with a specific mutation called F508del; this mutation is found in about 90% of CF patients. 

Apart from the AURORA trials, data from an open-label Phase 3 trial, in which all participants knew which treatment they were receiving, also supported the supplemental new drug application. In the study, 66 children, ages 6 to 11, were treated with oral Trikafta for 24 weeks. The therapy was found to be safe and well-tolerated in those younger patients.

In 2019, Trikafta was approved by the FDA to treat CF in patients 12 and older based on results from the AURORA trials that tested the safety and effectiveness of the therapy against placebo or Symdeko (tezacaftor/ivacaftor dual therapy). Results from the trials showed a significant improvement in lung function in patients treated with Trikafta.

“Since our initial approval of Trikafta in 2019, we have continued to work tirelessly to bring this medicine to those waiting as quickly as possible,” Bozic said. “We look forward to working with the Agency [FDA] as they review the application over the course of the coming months.”

Vertex also plans to submit a marketing authorization application for Trikafta use in patients ages 6 to 11 in the European Union in the first half of this year, with plans for similar regulatory filings in other countries, including Canada and Australia, in the coming months.