The European Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending the approval of Vertex Pharmaceuticals' Kalydeco (ivacaftor) for people with cystic fibrosis (CF) 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 CF ages 6 and older who have at least one copy of the G551D mutation, which is the most common gating mutation. The eight additional gating mutations included in today's recommendation 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.

"People with these additional gating mutations generally have severe cystic fibrosis, similar to patients with the most common gating mutation, G551D. There is an urgent need for new medicines that address the underlying cause of the disease for people with these mutations," said Jeffrey Chodakewitz, M.D., senior vice president and chief medical officer at Vertex. "Today's recommendation for the use of ivacaftor in people with eight additional gating mutations represents an important step toward our goal of helping more people with CF."

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. Kalydeco 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.

Today's CHMP opinion 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 CF ages 6 and older who have a non-G551D gating mutation. The first part of the study showed statistically significant improvements in lung function (FEV1), sweat chloride, BMI 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 showed that these improvements were maintained through 24 weeks of treatment with ivacaftor. The safety profile was similar to prior phase 3 studies of ivacaftor in people with the G551D mutation.

The CHMP's positive opinion will now be reviewed by the European Commission, which has the authority to approve medicines for the European Union. The European Commission generally follows the recommendation of the CHMP and typically issues marketing approval within three to four months.

The CHMP also issued a positive opinion recommending 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 Kalydeco 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 Kalydeco treatment groups) and met other eligibility criteria. Results from PERSIST demonstrated that the safety and efficacy of Kalydeco seen in the phase 3 STRIVE and ENVISION trials was maintained through nearly three years (144 weeks) in G551D patients.

Kalydeco (ivacaftor) is the first medicine to treat the underlying cause of CF in people with specific mutations in the CFTR gene. Known as a CFTR potentiator, Kalydeco is an oral medicine that aims to help the CFTR protein function more normally once it reaches the cell surface, to help hydrate and clear mucus from the airways. Kalydeco (150mg, q12h) was first approved by the US Food and Drug Administration in January 2012 for use in people with CF ages 6 and older who have at least one copy of the G551D mutation and in February 2014 for use in people with CF ages 6 and older who have the following additional CFTR mutations: G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P and G1349D. In Canada, K Kalydeco was first approved in November 2012 for use in people with CF ages 6 and older who have at least one copy of the G551D mutation and in June 2014 for use in people with CF ages 6 and older who have the following additional CFTR mutations: G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, G1349D and G970R.

Kalydeco was approved by the European Medicines Agency in July 2012, by the Therapeutic Goods Administration in Australia in July 2013, by Medsafe in New Zealand in December 2013 and by Swissmedic in Switzerland in January 2014 for use in people with CF ages 6 and older who have at least one copy of the G551D mutation in the CFTR gene.

Vertex retains worldwide rights to develop and commercialise Kalydeco.