Rare Daily Staff
The U.S. Food and Drug Administration expanded the approved use Vertex Pharmaceuticals’ Orkambi to include children ages 2 through 5 years with a specific genetic mutation causing cystic fibrosis, a rare and life-threatening genetic disease.
The expanded approval makes Orkambi the first medication approved to treat the underlying cause of CF in young children with two copies of the F508del-CFTR mutation.
Orkambi was first approved in 2015. It has been used in the United States for the treatment of CF in patients ages 6 and older who have two copies of the F508del–CFTR mutation. A Marketing Authorization Application line extension for Orkambi in children ages 2 through 5 years has been submitted to the European Medicines Agency with a decision anticipated in the first half of 2019.
CF is caused by a defective or missing cystic fibrosis transmembrane conductance regulator (CFTR) protein resulting from mutations in the CFTR gene. Children must inherit two defective CFTR genes — one from each parent — to have CF. There are approximately 2,000 known mutations in the CFTR gene.
Some of these mutations lead to CF by creating non-working or too few CFTR proteins at the cell surface. The defective function or absence of CFTR protein results in poor flow of salt and water into and out of the cell in a number of organs. In the lungs, this leads to the buildup of abnormally thick, sticky mucus that can cause chronic lung infections and progressive lung damage in many patients that eventually leads to death. The median age of death is in the mid-to-late 20s.
“For the first time, children ages 2 through 5 who have the most common form of CF have a treatment for the underlying cause of their disease,” said Reshma Kewalramani, executive vice president and chief medical officer at Vertex. “We believe it is important to treat the underlying cause of the disease as early as possible and this approval is another significant milestone in our journey to bring effective medicines to all people living with CF.”
The FDA based its expanded approval on a phase 3 open-label safety study in 60 patients that showed treatment with Orkambi was generally safe and well tolerated for 24 weeks, with a safety profile similar to that in patients ages 6 years and older. Improvements in sweat chloride, a secondary endpoint, were observed at week 24. Researchers also saw changes in key growth parameters, which were also secondary endpoints in the study.
The most common adverse event was cough (63 percent); most adverse events were mild or moderate in severity. Four patients experienced serious adverse events (2 pulmonary exacerbations, 1 gastroenteritis, 1 constipation) and three patients discontinued treatment due to treatment emergent adverse events or elevated liver function tests. These findings were presented at the 41stEuropean Cystic Fibrosis Society Conference in June 2018.
“Research suggests Orkambi could impact CF outcomes in patients as young as two years old,” John McNamara, Medical Director of the cystic fibrosis program at Children’s Minnesota hospital and lead study researcher. “This approval is a significant development that enables physicians to begin treating the underlying cause of the disease in this population earlier than ever before.”
August 8, 2018
Photo: Reshma Kewalramani, executive vice president and chief medical officer at Vertex.