On May 17, 2017, the FDA expanded the approved use of Kalydeco (ivacaftor) for treating cystic fibrosis. The approval triples the number of rare gene mutations that the drug can now treat, expanding the indication from the treatment of 10 mutations to 33. The expanded indication will affect another 3% of the cystic fibrosis population, impacting approximately 900 patients.
The agency based its decision, in part, on the results of laboratory testing, which it used in conjunction with evidence from earlier human clinical trials. Results from an in vitro cell-based model system have been shown to reasonably predict clinical response to Kalydeco. When additional mutations responded to Kalydeco in the laboratory test, researchers were able to extrapolate clinical benefit demonstrated in earlier clinical trials of other mutations. This resulted in the addition of gene mutations for which the drug is now indicated. The approach provides a pathway for adding additional, rare mutations of the disease, based on laboratory data.
“Many rare cystic fibrosis mutations have such small patient populations that clinical trial studies are not feasible,” said Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation and Research. “This challenge led us to using an alternative approach based on precision medicine, which made it possible to identify certain gene mutations that are likely to respond to Kalydeco.”
Cystic fibrosis is a rare disease that affects approximately 30,000 people in the United States. Cystic fibrosis affects the cells that produce mucus, sweat. and digestive juices. These secreted fluids are normally thin and slippery due to the movement of sufficient ions (chloride) and water in and out of the cells. People with the progressive disease have a defective cystic fibrosis transmembrane conductance regulator (CFTR) gene that cannot regulate the movement of ions and water, causing the secretions to become sticky and thick. The secretions build up in the lungs, digestive tract, and other parts of the body leading to severe respiratory and digestive problems, as well as other complications such as infections and diabetes.
Kalydeco helps the protein made by the CFTR gene function better and as a result, improves lung function and other aspects of cystic fibrosis, including weight gain. If the patient’s genotype is unknown, an FDA-cleared cystic fibrosis mutation test should be used to detect the presence of a CFTR mutation followed by verification with bi-directional sequencing when recommended by the mutation test instructions for use. Kalydeco is indicated for patients aged 2 and older who have one mutation in the CFTR gene that is responsive to drug treatment based on clinical and/or in vitro (laboratory) data.
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 transaminases (various enzymes produced by the liver) and pediatric cataracts.
Kalydeco serves as an example of how successful patient-focused drug development can provide greater understanding about a disease. For example, the Cystic Fibrosis Foundation maintains a 28,000-patient registry, including genetic data, which it makes available for research.
See the FDA Announcement
See also Medical Law Perspectives Report: Drugs, Dosage, and Damage: Physician Liability for Prescribing or Administering Medication