Vertex Pharmaceuticals Inc. recently confirmed that the European Commission has expanded the indication of Kalydeco^® (ivacaftor) to two more groups of patients: children ages 2 to 5 with cystic fibrosis (CF) who have at least one of nine gating mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene (G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N and S549R), and adults over age 18 with CF and a R117H gating mutation.

In Europe, approximately 125 CF children are thought to suffer from one of these nine gating mutations, and about 350 CF adults have the specific mutation identified by the Commission.

Ivacaftor had already been approved in the European Union (EU) for treating CF patients aged 6 or older who have one of the previously described gating mutations. With the new approval, Vertex can now begin the reimbursement process for each new indication, country-by-country. “These approvals bring us closer to our goal of developing new medicines to treat the underlying cause of cystic fibrosis for as many people as possible,” said Jeffrey Chodakewitz, MD, Executive Vice President and Chief Medical Officer at Vertex.

Cystic Fibrosis develops due to a defective or missing CFTR protein resulting from mutations in the CFTR gene. Patients who have gating mutations, a R117H mutation for instance, have their CFTR protein reaching the cell surface but not working properly afterward. Known as a CFTR motivator, ivacaftor is an oral intake drug designed to help CFTR proteins open more often at the cell surface in order to improve the transport of salt and water through the cell membrane, which benefits hydration and the clearing of airway mucus. Ivacaftor is the first treatment for treating the underlying cause of CF in people with particular mutations in the CFTR gene.

Ivacaftor in Children (2-5) with Gating Mutations

“We know that the progressive damage caused by cystic fibrosis can start at birth, so early treatment is critical to offering the best chance of improving long-term outcomes,” said Professor Jane Davies, MD, of the Royal Brompton Hospital and Imperial College, London, and a lead principal investigator on the ivacaftor Phase 3 study in children ages 2 to 5. “Today’s approval means that, for the first time, we’ll be able to treat the underlying cause of the disease in very young children, possibly even before they experience severe signs and symptoms of CF.”

The decision to authorize ivacaftor for treatments in younger children with gating mutations was based on data results of an earlier, 24-week open-label Phase 3 study designed to evaluate the safety and pharmacokinetics of weight-based dosing of ivacaftor (50 mg or 75 mg twice daily) in patients from 2- to 5-years-old. The study also included children from ages 6 to 11 who weighed less than 25 kg. Children involved in the trial were given a weight-based granule formulation of ivacaftor, mixed in soft foods or liquids, in strengths of 50 mg or 75 mg.

“Expanding the use of ivacaftor will allow younger children with cystic fibrosis to benefit from earlier treatment of the underlying cause of their disease,” added Dr. Chodakewitz.

Ivacaftor in Adults with a R117H Mutation

The European Commission decided to authorize ivacaftor in adults with an R117H mutation based on formerly announced data from a Phase 3 clinical trial that enrolled 69 people. “While people with an R117H mutation can exhibit a wide range of severity in their CF, once their disease begins to progress, lung function decline can be severe,” explained Dr. Chodakewitz. “This approval is an important advance for adults with an R117H mutation who will now have a medicine to treat the underlying cause of their disease for the first time.”