FDA OKs Expanded Use of Ivacaftor (Kalydeco) in Cystic Fibrosis

Megan Brooks

February 25, 2014

The US Food and Drug Administration (FDA) has approved a supplemental new drug application (sNDA) allowing use of ivacaftor (Kalydeco, Vertex Pharmaceuticals) in patients aged 6 years and older with cystic fibrosis (CF) caused by any of 8 additional mutations in the CF transmembrane conductance regulator (CFTR) gene.

Defects in the CFTR gene are the basis of CF. Ivacaftor was first approved in January 2012 for patients with CF who were aged 6 years and older and had at least 1 copy of the G551D mutation in the CTFR gene, as reported by Medscape Medical News.

With the new approval of the sNDA, ivacaftor is now indicated for use in patients with CF who are 6 years and older with any of these other 8 CFTR gene mutations: G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, and G1349D.

Roughly 150 people aged 6 years and older in the United States have 1 of the additional 8 mutations for which ivacaftor is now approved, according to Vertex.

CF is characterized by abnormal transport of chloride and sodium across an epithelium, leading to thick, viscous secretions resulting from mutations in the CFTR gene. Ivacaftor targets the defective CFTR protein and facilitates increased chloride transport by potentiating the channel-open probability (or gating) of the protein, Vertex said.

Ivacaftor was given breakthrough therapy designation by the FDA in late 2012.

Vertex said the sNDA approval was based on data from a randomized controlled phase 3 study involving 39 people with CF who had any 1 of the following mutations: G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, G1349D, or G970R.

"The study showed statistically significant improvements in lung function...for people in the overall study population who received ivacaftor, and the safety profile was similar to prior Phase 3 studies in people with the G551D mutation," Vertex said.

However, based on data from 4 patients with the G970R mutation, the efficacy of ivacaftor in patients with this mutation could not be established to support approval in the United States, the company said. Vertex estimates that about 10 people with CF have the G970R mutation worldwide, including 2 people in the United States.


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