Expanded Approval of CF Treatment for Children Aged 6+

Patients Had Improved Lung Function, Fewer Exacerbations

The FDA has expanded the indication for tezacaftor/ivacaftor tablets (Symdeko, Vertex Pharmaceuticals Incorporated) for the treatment of pediatric patients aged 6 years and older with cystic fibrosis (CF) who have certain genetic mutations. In 2018, the agency approved tezacaftor/ivacaftor for patients aged 12 and older who had the same genetic mutations.

Cystic fibrosis, a serious genetic disorder that creates a buildup of thick mucus in the lungs, digestive tract, and other parts of the body, is caused by a defective protein resulting from mutations in the CF transmembrane conductance regulator (CFTR) gene. Patients develop severe respiratory and digestive problems, and infections and diabetes.

There are approximately 2,000 known mutations of CFTR. Tezacaftor/ivacaftor is used to treat patients with two copies of the most common mutation–the F508del–or with at least one of the mutations that responds to the drug’s active ingredients, based on in vitro data and/or clinical evidence. 

The efficacy of tezacaftor/ivacaftor in patients with CF aged 12 years and older was evaluated in three phase 3, double-blind, placebo-controlled trials. Patients demonstrated improvements in lung function and other important measures, including a reduction in exacerbations. 

Tezacaftor/ivacaftor’s safety in patients aged 6 to less than 12 years with CF was supported by data from a 24-week, open-label treatment period with 70 patients; this study had similar results to trials in patients with CF ages 12 and older. 

The prescribing information includes warnings about elevated transaminase enzymes in people taking tezacaftor/ivacaftor and in those using inducers for cytochrome P450 3A4 (CYP3A), and also for cataract risk in pediatric patients. The most common side effects include headache, nausea, sinus congestion, and dizziness.

The FDA granted this application a priority review designation. 

Source: FDA, June 21, 2019