FDA Expands Use of Symdeko for Cystic Fibrosis to Younger Children

Megan Brooks


June 21, 2019

The US Food and Drug Administration (FDA) has expanded the indication for tezacaftor/ivacaftor tablets (Symdeko, Vertex Pharmaceuticals) to children as young as 6 years with cystic fibrosis (CF) who have two copies of the F508del mutation in the CF transmembrane conductance regulator (CFTR) gene or at least one mutation that is responsive to tezacaftor/ivacaftor.

Last year, the FDA approved tezacaftor/ivacaftor tablets for children as young as 12 years with CF and the same specific genetic mutations, as reported by Medscape Medical News.

"We've seen the clinical impact of Symdeko in people with CF aged 12 years and above, and this approval marks a crucial milestone for patients ages 6 through 11 years who may benefit from CFTR modulation, enabling us to treat the basic defect in CF at an earlier stage of disease," Seth Walker, MD, of the University Hospitals Rainbow Babies & Children's Hospital, Cleveland, Ohio, said in a Vertex news release.

"Symdeko is an important treatment option for eligible people with CF who either never started or have discontinued another CFTR modulator," said Walker.

CF is a rare, life-shortening genetic disease that affects approximately 75,000 people in North America, Europe, and Australia. The disease is caused by a defective or missing CFTR protein resulting from mutations in the CFTR gene, which leads to formation of thick mucus that builds up in the lungs, digestive tract, and other parts of the body, causing severe respiratory and digestive problems, as well as infections.

Ivacaftor enhances the function of the CFTR protein once it reaches the cell surface to improve the transport of salt and water across the cell membrane, which helps hydrate and clear mucus from the airways. Tezacaftor increases the amount of mature CFTR at the cell surface by targeting the processing and trafficking defect of the CFTR protein.

"[The] approval of Symdeko for children as young as 6 years old provides an important treatment option for younger patients, and also provides more context on the safety and dosing specific to this population," Banu Karimi-Shah, MD, acting deputy director of the Division of Pulmonary, Allergy, and Rheumatology Products in the FDA's Center for Drug Evaluation and Research, said in a statement.

The efficacy of tezacaftor/ivacaftor in children with CF aged 12 years and older was assessed in three phase 3, double-blind, placebo-controlled trials, which demonstrated improvements in lung function and other key measures of the disease, including a reduction in exacerbations.

The efficacy of the drug in children as young as age 6 was extrapolated from patients age 12 years and older, with additional support from data in patients aged 6 to 12 years, the FDA said.

The safety profile of tezacaftor/ivacaftor in children as young as 6 is similar to that in older children. The most common adverse effects include headache, nausea, sinus congestion, and dizziness. The safety and efficacy of the drug has not been studied in children younger than 6 years.

In connection with this expanded indication, the company has made an additional dosage strength of Symdeko tablets available (tezacaftor 50 mg/ivacaftor 75 mg and ivacaftor 75 mg).

Children aged 6 to younger than 12 years weighing less than 30 kg take one tablet (containing tezacaftor 50 mg/ivacaftor 75 mg) in the morning and one tablet (containing ivacaftor 75 mg) in the evening, approximately 12 hours apart.

Full prescribing information is available on the Vertex website.

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