Vertex Receives European Approval for KALYDECO (ivacaftor) in Eight Non-G551D Gating Mutations

In Press Release by Cecile

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July 31st, 2014

-In Europe, approximately 250 people ages 6 and older have one of 8 additional gating mutations-

-KALYDECO is the first medicine to treat the underlying cause of CF in people with specific non-G551D gating mutations

Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that the European Commission has approved 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. Today’s approval follows the positive opinion from the Committee for Medicinal Products for Human Use (CHMP) in June 2014. KALYDECO was first approved in Europe in July 2012 for people with CF ages 6 and older who have the G551D mutation, which is the most common gating mutation. The eight additional gating mutations included in today’s 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.

“Today’s approval in people with additional gating mutations marks another step toward our goal of helping more people with this disease,” said Simon Bedson, Senior Vice President and International General Manager at Vertex. “We are committed to working closely with the appropriate national authorities to make KALYDECO available for these patients as soon as possible.”

Today’s 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 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, 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 showed 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.

“By treating the underlying cause of cystic fibrosis, KALYDECO has changed the way we treat patients with the most common gating mutation, G551D. In general, people with other gating mutations have similarly severe disease to people with the G551D mutation and have an urgent need for new medicines that address the underlying cause of the disease,” said Kris De Boeck, M.D., Ph.D., Professor of Pediatric Pulmonology, University Hospital Gasthuisberg, Leuven, Belgium, and President-Elect of the European Cystic Fibrosis Society. “In the Phase 3 study in people with non-G551D gating mutations, KALYDECO led to rapid, significant and sustained improvements in lung function and other measures of disease.”

In addition, the CHMP 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 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.

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.