The Food and Drug Administration (FDA) has expanded the approval of Trikafta® (elexacaftor/tezacaftor/ivacaftor and ivacaftor) to include patients with cystic fibrosis (CF) aged 6 to 11 years 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 12 years of age and older.
The approval was based on data from a 24-week multicenter, open-label phase 3 study (ClinicalTrials.gov Identifier: NCT03691779) that evaluated the efficacy and safety of Trikafta in 66 children 6 to 11 years of age with CF who were either homozygous for the F508del mutation or heterozygous for the F508del mutation and 1 minimal function mutation. Patients weighing less than 30kg received 50% of the Trikafta adult dose and those weighing greater than or equal to 30kg received the full adult dose. The primary endpoints were safety and tolerability.
Results showed that treatment with Trikafta was well tolerated and generally consistent with that observed in older patients. The most common adverse events reported were cough, headache, and pyrexia, which were mild or moderate in severity.
Additionally, treatment with Trikafta led to improvements in the mean absolute change from baseline to week 24 for the following secondary endpoints: 10.2 percentage points in ppFEV1 (95% CI, 7.9-12.6), Cystic Fibrosis Questionnaire–Revised respiratory domain score (7.0 points; 95% CI, 4.7-9.2), lung clearance index at 2.5 of starting concentration (-1.71 units; 95% CI, -2.11, -1.30), and sweat chloride concentration (-60.9 mmol/L; 95% CI, -63.7, -58.2). Additionally, body mass index increased over the 24-week treatment period.
An additional dosage strength of Trikafta containing elexacaftor 50mg, tezacaftor 25mg, and ivacaftor 37.5mg co-packaged with ivacaftor 75mg is now available. The product is also supplied as elexacaftor 100mg, tezacaftor 50mg, and ivacaftor 75mg co-packaged with ivacaftor 150mg.
- Vertex announces U.S. FDA approval for Trikafta® (elexacaftor/tezacaftor/ivacaftor and ivacaftor) in children with cystic fibrosis ages 6 through 11 with certain mutations. [press release]. Boston, MA: Vertex Pharmaceuticals Incorporated; June 9, 2021.
- Zemanick ET, Taylor-Cousar JL, Davies J, et al. 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. American Journal of Respiratory and Critical Care Medicine. doi: 10.1164/rccm.202102-0509OC.
- Trikafta® [package insert]. Boston, MA: Vertex Pharmaceuticals Incorporated; 2021.