FDA Expands Use of Kalydeco to Treat Cystic Fibrosis Caused by Rare Mutations

The FDA has expanded the approved uses of Kalydeco (ivacaftor), which is used to treat cystic fibrosis, so it can now be used by patients with any of 33 rare gene mutations.

When Kalydeco was first approved in 2012, it was indicated for the treatment of 10 mutations that cause cystic fibrosis. The rare disease is caused by a defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which regulates the movement of ions and water in and out of cells. The mutation causes secretions to accumulate in the lungs and digestive tract, resulting in severe respiratory and digestive problems and potentially contributing to complications like diabetes or infections.

About 30,000 Americans are living with cystic fibrosis, and the expanded indication to 23 additional types of gene mutations means that 900 more people in the United States can use Kalydeco to treat their cystic fibrosis. For years, the small pool of patients with the disease made it difficult to determine which indications were appropriate for the drug, according to Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research.

“Many rare cystic fibrosis mutations have such small patient populations that clinical trial studies are not feasible,” Woodcock said in the press release announcing the expanded approval. “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.”

Laboratory researchers used in vitro cells to assess which mutations responded to Kalydeco, which serves as a predictor of response to treatment. Regulators then could extend the clinical results seen in the drug’s prior clinical trials, where it successfully treated patients with the other gene mutations, to the mutations that had responded in the laboratory.

Kalydeco works by improving the functioning of the proteins manufactured by the CTFR gene, which helps it better regulate the movement of fluids between cells and reduces the respiratory symptoms. Patients can undergo a mutation test to determine if their particular gene mutation is one that will respond to Kalydeco.

According to a press release from Vertex, the manufacturer of Kalydeco, the expanded approval is a significant step towards increasing access to treatment for those living with cystic fibrosis.

“We are encouraged by the FDA's willingness to explore innovative ways to make highly effective medicines like Kalydeco with a well-established safety profile available to more people who are in urgent need,” said Jeffery Chodakewitz, MD, executive vice president and chief medical officer. “We will continue to work closely with the FDA to bring Kalydeco to more people with responsive mutations who are still in need as rapidly as possible."