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Cystic fibrosis: European approval for Kalydeco in eight non-G551D gating mutations

The European Commission has approved Kalydeco ( Ivacaftor ) for people with cystic fibrosis ages 6 and older who have one of eight non-G551D gating mutations in the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene.
Kalydeco was first approved in Europe in July 2012 for people with cystic fibrosis ages 6 and older who have the G551D mutation, which is the most common gating mutation.
The eight additional gating mutations included in the approval are: G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P and G1349D.
In Europe, approximately 250 people ages 6 and older have one of these non-G551D gating mutations.

The approval is based on previously announced data from the first part of a phase 3, two-part, randomised, double-blind, placebo-controlled, cross-over study of 39 people with cystic fibrosis ages 6 and older who have a non-G551D gating mutation.
The first part of the study has shown statistically significant improvements in lung function ( FEV1 ), sweat chloride, body mass index and CFQ-R scores.
Data from the second part of the study were presented at the European Cystic Fibrosis Society Conference in June 2014 and have shown that these improvements were maintained through 24 weeks of treatment.
The safety profile was similar to prior phase 3 studies of Kalydeco in people with the G551D mutation.

In addition, the CHMP ( Committee for Medicinal Products for Human Use ) has approved the inclusion of data from the long-term follow-up PERSIST study in the Kalydeco label.
PERSIST is a Phase 3, open-label, 96-week, rollover extension trial that evaluated the long-term safety and durability of treatment with Ivacaftor by enrolling people ages 6 and older with at least one copy of the G551D mutation who completed 48 weeks of treatment in the phase 3 ENVISION and STRIVE studies ( placebo and Ivacaftor treatment groups ) and met other eligibility criteria.
Results from PERSIST have demonstrated that the safety and efficacy of Ivacaftor seen in the Phase 3 STRIVE and ENVISION trials was maintained through nearly three years ( 144 weeks ) in G551D patients.

Cystic fibrosis is caused by a defective or missing CFTR protein that results from mutations in the CFTR gene. CFTR proteins act as channels at the cell surface that control the flow of salt and water into and out of the cell.
In people with gating mutations, the CFTR protein at the cell surface is defective and does not work properly, causing abnormally thick, sticky mucus to build up in the lungs.

The digestive tract and a number of other organs are also affected.

Kalydeco, an oral medicine known as a CFTR potentiator, helps the CFTR protein function more normally once it reaches the cell surface. It targets the abnormal CFTR protein channels and opens them to allow chloride ions to move into and out of the cell, which helps thin the mucus so it can hydrate and protect the airways. ( Xagena )

Source: Vertex Pharmaceuticals, 2014