The Food and Drug Administration (FDA) has expanded the approval of Trikafta® (elexacaftor/tezacaftor/ivacaftor and ivacaftor) to include children with cystic fibrosis (CF) ages 2 through 5 who have at least 1 F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene or a mutation in the CFTR gene that is responsive based on in vitro data. Previously, Trikafta was only approved for CF patients 6 years of age and older.
The approval was based on data from a 24-week open-label, two-part phase 3 study (ClinicalTrials.gov Identifier: NCT04537793) that evaluated the efficacy and safety of Trikafta in 75 children 2 to less than 6 years of age with CF who had at least 1 F508del mutation or a mutation known to be responsive to Trikafta.
Results showed patients experienced clinically meaningful reductions in sweat chloride concentration (a measure of CFTR function; mean absolute change in sweat chloride from baseline through week 24: -57.9 mmol/L [95% CI, -61.3, -54.6]) and lung clearance index (mean change from baseline through week 24: -0.83 units [95% CI, −1.01, −0.66]). Treatment with Trikafta was generally well tolerated and consistent with that observed in older patients. The most common adverse events reported were cough, fever, and rhinorrhea.
“Early intervention with CFTR modulator therapies like Trikafta can offer the potential to improve the trajectory of CF lung disease,” said Jennifer Goralski, MD, Assistant Professor of Medicine and Pediatrics, Co-Director, Adult Cystic Fibrosis Center, University of North Carolina School of Medicine, and a lead Principal Investigator in the Trikafta 2- to 5-year-old pivotal clinical trial. “With this approval, we now have the ability to treat young children with Trikafta and can proactively address the underlying cause of their disease.”
Trikafta is currently available in tablet form. A new oral granules formulation has been approved and is supplied in morning and evening unit-dose packets; it is expected to be available within the next few weeks.
- Vertex announces US FDA approval for Trikafta® (elexacaftor/tezacaftor/ivacaftor and ivacaftor) in children with cystic fibrosis ages 2 through 5 with certain mutations. News release. Vertex. Accessed April 26, 2023. https://www.businesswire.com/news/home/20230426005815/en/Vertex-Announces-U.S.-FDA-Approval-for-TRIKAFTA%C2%AE-elexacaftortezacaftorivacaftor-and-ivacaftor-in-Children-With-Cystic-Fibrosis-Ages-2-Through-5-With-Certain-Mutations.
- Goralski JL, Hoppe JE, Mall MA, et al. Phase 3 open-label clinical trial of elexacaftor/tezacaftor/ivacaftor in children aged 2 through 5 years with cystic fibrosis and at least one F508del allele. American Journal of Respiratory and Critical Care Medicine. Published March 15, 2023. doi:10.1164/rccm.202301-0084OC
- Trikafta. Package insert. Vertex; 2023. Accessed April 26, 2023. https://pi.vrtx.com/files/uspi_elexacaftor_tezacaftor_ivacaftor.pdf.