FDA Triples Uses for Cystic Fibrosis Drug

The US Food and Drug Administration (FDA) has expanded the approved use of Vertex Pharmaceuticals’ ivacaftor (Kalydeco) for the treatment of cystic fibrosis (CF).

The approval triples the number of rare gene mutations that the drug can now treat from 10 mutations to 33 mutations. The FDA’s decision was based in part on results from laboratory testing, which the agency used in conjunction with evidence from earlier human clinical trials. This approach provides a pathway for adding additional, rare mutations of the disease based on laboratory data, according to an FDA statement.

“Many rare cystic fibrosis mutations have such small patient populations that clinical trial studies are not feasible,” said Janet Woodcock, MD, 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 [ivacaftor].”

Vertex Pharmaceuticals is continuing discussions with the FDA concerning the approval for additional people who have mutations responsive to the drug, including one of 5 “splice” mutations, according to a company statement. These 5 mutations were evaluated as part of the phase III EXPAND study, in which the ivacaftor monotherapy arm met its primary efficacy endpoint while being generally well tolerated. More than 600 people ages 2 and older in the US have one of these mutations, the statement read.

“CF treatment has advanced rapidly, but there is need for broader access to these important medicines and development of additional medicines remains urgent,” said Patrick Flume, MD, director of the Medical University of South Carolina Cystic Fibrosis Center. “The use of in vitro data to support this approval is an important step forward in making medicines like Kalydeco [ivacaftor] available to more patients, especially those with rare mutations.”

Results from an in vitro cell-based model system have been shown to reasonably predict clinical response to ivacaftor. When additional mutations responded to ivacaftor in the laboratory test, researchers were thus able to extrapolate clinical benefits demonstrated in earlier clinical trials of other mutations. This resulted in the addition of gene mutations for which the drug is now indicated.

Ivacaftor is available as tablets or oral granules taken two times a day with fat-containing food. It helps the protein made by the cystic fibrosis transmembrane conductance regulator (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.

Common side effects of ivacaftor include headache; upper respiratory tract infection including sore throat, nasal or sinus congestion, or runny nose; abdominal pain; diarrhea; rash; nausea; and dizziness.


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