Vertex’ Orkambi Approved in Europe for Treatment of Children with Cystic Fibrosis Ages 1 to 2 Years Old

The European Commission approved the label extension for Vertex Pharmaceuticals’ combination treatment for cystic fibrosis to include infants between the ages of 1 and 2.

The EC granted approval of Orkambi (lumacaftor/ivacaftor) for the treatment of children with cystic fibrosis ages 1 to less than 2 years old who have two copies of the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, the most common form of the disease.

“This approval will offer some of the youngest children with cystic fibrosis the chance of improved outcomes, by treating their disease at a young age,” said Carmen Bozic, executive vice president, Global Medicines Development and Medical Affairs, and chief medical officer, Vertex. “With this important milestone, we move ever closer to our goal of providing medicines that treat the underlying cause of CF to all people living with the disease.”

Cystic fibrosis (CF) is a rare, life-shortening genetic disease affecting more than 88,000 people globally. CF is a progressive, multi-organ disease that affects the lungs, liver, pancreas, GI tract, sinuses, sweat glands and reproductive tract. CF is caused by a defective and/or missing CFTR protein resulting from certain mutations in the CFTR gene. Children must inherit two defective CFTR genes — one from each parent — to have CF, and these mutations can be identified by a genetic test. While there are many different types of CFTR mutations that can cause the disease, the vast majority of people with CF have at least one F508del mutation. CFTR mutations lead to CF by causing CFTR protein to be defective or by leading to a shortage or absence of CFTR protein at the cell surface. The defective function and/or absence of CFTR protein results in poor flow of salt and water into and out of the cells in a number of organs. In the lungs, this leads to the buildup of abnormally thick, sticky mucus, chronic lung infections and progressive lung damage that eventually leads to death for many patients. The median age of death is in the early 30s.

In people with two copies of the F508del mutation, the CFTR protein is not processed and trafficked normally within the cell, resulting in little to no CFTR protein at the cell surface.

Orkambi is an oral medicine that is a combination of lumacaftor and ivacaftor. Lumacaftor is designed to increase the amount of mature protein at the cell surface by targeting the processing and trafficking defect of the F508del-CFTR protein. Ivacaftor, which is known as a CFTR potentiator, is designed to facilitate the ability of CFTR proteins to transport salt and water across the cell membrane. The combined actions of lumacaftor and ivacaftor help hydrate and clear mucus from the airways.

“CF symptoms and organ damage can manifest very early in life, so it is crucial to start treatment as early as possible,” said Silvia Gartner, specialist in Pediatrics and Pneumonology, coordinator of the Pediatric Cystic Fibrosis Center, Barcelona. “Today’s approval provides us with a medicine that gives a window of opportunity to possibly delay the onset of CF for these very young eligible children.”

Orkambi has also been approved by regulatory authorities in the U.S., in Great Britain, Australia, and Canada, for people with CF and two copies of the F508del mutation in the CFTR gene, ages 1 and above.

Photo: Carmen Bozic, executive vice president, Global Medicines Development and Medical Affairs, and chief medical officer, Vertex