BOSTON and SILVER SPRING, Md.—The U.S. Food and Drug Administration (FDA) announced today the expanded indication for Symdeko (a combination of tezacaftor and ivacaftor) tablets for treatment of pediatric patients ages 6 years and older with cystic fibrosis who have two copies of the F508del-CFTR mutation, or who have at least one mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that is responsive to Symdeko. The application received Priority Review, and approval was granted to Vertex Pharmaceuticals Incorporated.
Last year the FDA approved Symdeko to treat patients ages 12 and older who had the same specific genetic mutations. An additional dosage strength of Symdeko tablets is now available (tezacaftor 50 mg/ivacaftor 75 mg and ivacaftor 75 mg) in connection with this approval.
“Decades ago, patients with cystic fibrosis were generally expected to live until 10 years of age, with few surviving into their teenage years. Since then, wide-ranging research on the disease resulted in more treatments for this debilitating disease that have extended life expectancy and improved quality of life for patients, but there is still no cure,” said Banu Karimi-Shah, M.D., acting deputy director of the Division of Pulmonary, Allergy, and Rheumatology Products in the FDA’s Center for Drug Evaluation and Research.
“Based on their individual genetic makeup, individuals may respond differently to certain drugs, so it is important to provide a variety of options. Today’s 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,” Karimi-Shah continued. “The FDA remains committed to advancing novel treatment options for areas of unmet patient need, particularly in diseases impacting children.”
Cystic fibrosis is caused by a defective protein that results from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. There are approximately 2,000 known mutations of the CFTR gene. Symdeko is used to treat patients who have two copies of the most common type of mutation – the F508del mutation – or who have at least one of the mutations in the CFTR gene that is responsive to the active ingredients in Symdeko based on in vitro data and/or clinical evidence.
“Today’s expanded approval of Symdeko in children ages 6 through 11 is an important step in our efforts to continue to bring treatment options to the youngest patients possible and importantly brings us closer to our goal of developing medicines for all people living with CF,” said Reshma Kewalramani, M.D., executive vice president and chief medical officer at Vertex.
The efficacy of Symdeko in patients with cystic fibrosis age 12 years and older was evaluated 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 in patients ages 6 to 12 was extrapolated from patients age 12 years and older, with additional support from data in patients age 6 to 12 years.
Vertex completed a 24-week Phase 3 open-label, multicenter study to evaluate the pharmacokinetics, safety and tolerability of tezacaftor/ivacaftor and ivacaftor in 70 cystic fibrosis patients ages 6 through 11 years in the U.S. and Canada. The regimen was generally well tolerated, and safety data were similar to what was observed in previous studies of patients aged 12 years and older. The full data from this study will be published later this year.
“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,” added Seth Walker, M.D., University Hospitals of Cleveland, Cleveland Medical Center, Rainbow Babies and Children’s Hospital. “Symdeko is an important treatment option for eligible people with CF who either never started or have discontinued another CFTR modulator.”
Symdeko/Symkevi (tezacaftor/ivacaftor and ivacaftor) is already approved in the U.S., Canada, Switzerland, Australia and the EU for the treatment of CF in patients ages 12 years and older with certain mutations. Vertex plans to submit an application for the use in patients ages 6 through 11 years in the European Medicines Agency in the second half of 2019.
