FDA expands approval of cystic fibrosis treatment to include pediatric patients as young as 6 years old

Reviewed by Alina Shrourou, B.Sc. (Editor)Jun 22 2019

The U.S. Food and Drug Administration today expanded the indication for Symdeko (a combination of tezacaftor/ivacaftor) tablets for treatment of pediatric patients ages 6 years and older with cystic fibrosis who have certain genetic mutations. Last year, the FDA approved Symdeko to treat patients ages 12 and older who had the same specific genetic mutations.

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.

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. The FDA remains committed to advancing novel treatment options for areas of unmet patient need, particularly in diseases impacting children."

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

Cystic fibrosis is a serious genetic disorder that results in the formation of thick mucus that builds up in the lungs, digestive tract and other parts of the body. It leads to severe respiratory and digestive problems as well as other complications such as infections and diabetes. 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 - 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. Patients with cystic fibrosis and their caregivers should speak with a health care professional and have tests performed to understand which gene mutations patients have and whether Symdeko is likely to work for them.

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 (a worsening of symptoms requiring treatment). 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.

The safety of Symdeko to treat cystic fibrosis patients age 6 to less than 12 years was supported by data from a study that included a 24-week, open-label treatment period with 70 cystic fibrosis patients ages 6 to less than 12, and had similar observations of safety to clinical trials in ages 12 and older. Symdeko should always be taken with food that contains fat and never in combination with certain antibiotics, seizure medicines, St. John's wort, or food containing grapefruit or Seville oranges, as indicated on the label.

The prescribing information for Symdeko includes warnings related to elevated enzymes in the liver (transaminases) in people taking Symdeko, for those who use inducers for another liver enzyme called Cytochrome P450 3A4 (CYP3A), and for the risk of cataracts in pediatric patients. Patients and their caregivers should speak with a health care professional about these risks and any medicines they take before starting Symdeko. The most common side effects include headache, nausea, sinus congestion and dizziness.

The safety and efficacy of Symdeko in patients with cystic fibrosis younger than 6 years of age have not been studied.

The FDA granted this application Priority Review. The approval of Symdeko was granted to Vertex Pharmaceuticals Incorporated.