RARE Daily

FDA Approves Vertex’s Orkambi in Children with Cystic Fibrosis Ages 12 to Less Than 24 Months

September 6, 2022

The U.S. Food and Drug Administration approved expanded use of Orkambi to include children with cystic fibrosis ages 12 to less than 24 months who are homozygous for the F508del mutation (F/F genotype) in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.

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

Orkambi was previously approved by the FDA for use in people with cystic fibroses ages 2 years and older with two copies of the F508del mutation. Orkambi (lumacaftor/ivacaftor) was first approved in 2015 in the U.S. and is now available in more than 30 countries. With this approval, approximately 300 children with two copies of the F508del mutation will have a medicine to treat the underlying cause of their disease for the first time.

“Treating children with cystic fibrosis as early in life as possible is critically important, because early treatment has the potential to slow the progression of this devastating disease,” said Carmen Bozic, executive vice president, Global Medicines Development and Medical Affairs, and chief medical officer of Vertex. “Today’s approval is another important step on our journey to reach people of all ages living with cystic fibrosis who may benefit from our medicines.”

Cystic fibrosis (CF) is a rare, life-shortening genetic disease affecting more than 83,000 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 the 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.

The approval in children ages 12 to less than 24 months is based on a 24-week, phase 3, open-label, multi-center study in 46 children ages 1 to less than 2 years with the F/F genotype. Orkambi was generally well tolerated, and the safety profile and pharmacokinetics were similar to that observed in studies in patients ages 2 years and older. Additional study results, including reductions in sweat chloride concentration, suggest the potential for CF disease modification with the use of Orkambi.

Author: Rare Daily Staff

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