FDA Says “No” to Expanded Indication for Cystic Fibrosis Drug Ivacaftor (Kalydeco)

Company wants to increase targeted gene mutations from 10 to 23

Vertex Pharmaceuticals has received a complete response letter from the FDA in answer to the company’s supplemental new drug application (sNDA) for the use of ivacaftor (Kalydeco) in patients 2 years of age and older with cystic fibrosis (CF) who have one of 23 residual function mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The FDA determined that it cannot approve the application in its present form. Vertex plans to meet with the FDA to discuss the matter.

CF is caused by defective or missing CFTR proteins resulting from mutations in the CFTR gene. The defective or missing proteins result in poor flow of salt (chloride) and water into and out of the cell in several organs, including the lungs. Chloride transport is a marker of the function of the CFTR protein at the cell surface.

Ivacaftor, which received a breakthrough therapy designation from the FDA in 2013, is currently approved in the U.S. to treat patients 2 years of age and older who have one of 10 mutations in the CFTR gene (G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R, or R117H). The treatment is not currently indicated for patients with CF due to other mutations in the CFTR gene. Ivacaftor is not effective in patients with CF with two copies of the F508del mutation (F508del/F508del) in the CFTR gene. It is not known whether ivacaftor is safe and effective in children under 2 years of age.

Source: Vertex Pharmaceuticals; February 5, 2016.