FDA Expands Kalydeco (Ivacaftor) Indication to Treat Additional Mutations in Cystic Fibrosis Patients Age 2 Years and Older Using an Alternative to Human Clinical Studies

On May 17, 2017, the US Food & Drug Administration (FDA) expanded the approved indication for Kalydeco (ivacaftor) for the treatment of cystic fibrosis (CF) in patients age 2 years and older who have one mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that is responsive to ivacaftor potentiation based on clinical and/or in vitro assay data. Kalydeco was previously approved for use in patients with one of ten different types of mutations in the CFTR, which occur in about 4 percent of CF patients. This approval expands the number of approved mutations from 10 to 33 and also provides a pathway to add additional rare CF mutations based on laboratory data. 

The CFTR gene was identified almost 30 years ago and knowledge on the resultant CFTR channel’s structure and function, the clinical aspects of the disease and what causes it, and data on thousands of CF patients and their mutations have been accumulated. In addition, there is clear understanding of Kalydeco’s mechanism of action and a sufficient understanding of the risk/benefit profile for Kalydeco has been established from years of patient exposures for the previously approved mutations.

The expanded indication for Kalydeco was based on an alternative to human clinical studies, which are not feasible since many rare CF mutations have such small patient populations. Therefore, supporting information for the expanded indication relied on data from an in vitro cell-based model system built on Kalydeco’s existing knowledge base. Kalydeco’s ability to improve the function of the defective protein has been shown in a reliable in vitro cell model and was determined to reasonably accurately predict the likely response of patients with mutations not included in the initial clinical trials. Data from this model was deemed sufficient to determine whether certain populations with CF would likely respond to Kalydeco.

The recommended dose of KALYDECO for both adults and pediatric patients ages 6 years and older is one 150 mg tablet taken orally every 12 hours with fat-containing food. The recommended dose of KALYDECO (oral granules) for patients ages 2 to less than 6 years is 100 mg/day if body weight is less than 14 kg and 150 mg/day if body weight is 14 kg or greater administered just before or just after fat-containing food.

Common side effects of KALYDECO include headache; upper respiratory tract infection (common cold) including sore throat, nasal or sinus congestion, or runny nose; stomach (abdominal) pain; diarrhea; rash; nausea; and dizziness. KALYDECO is associated with risks including elevated liver transaminases and pediatric cataracts. Co-administration with strong CYP3A inducers (e.g., rifampin) substantially decreases exposure of KALYDECO, which may diminish effectiveness, and is therefore not recommended.

Full prescribing information is available at https://go.usa.gov/xNkCJ