An update of another Phase 3 trial’s findings showed that Orkambi is more effective when CF patients start with a half dose, then step up to a full one, rather than starting with a full dose.
CF patients have a faulty protein known as CFTR — for cystic fibrosis transmembrane conductance regulator. The abnormality prevents the protein from going to the surface of a cell, where it can control water flux and help ions enter and leave the cell. The abnormality leads to the thickening of the mucus lining the lung’s wall, increasing a patient’s risk of developing a lung infection.
Orkambi is composed of two substances that help CF patients produce thinner mucus. Lumacaftor helps transport CFTR protein to cells’ surface, and ivacaftor facilitates the proper functioning of CFTR when it reaches the surface.
“In nearly 20 years of research in collaboration with the cystic fibrosis community, we’ve made remarkable progress in efforts to change the way CF is treated by developing medicines that address the underlying cause of the disease, not just the symptoms.” Jeffrey Chodakewitz, executive vice president of Vertex, said in a press release.
One trial (NCT02514473) covered 204 children with CF, aged 6 to 11. The CFTR gene is defective in cystic fibrosis, and the youngsters had two copies of the gene’s F508del mutation.
Researchers randomly assigned the children to either twice-a-day doses of Orkambi or a placebo for 24 weeks.
Orkambi significantly improved their lung function, their ability to clear mucus and other substances from their lungs, and the amount of chloride ions they eliminated through sweating, compared with a placebo.
Vertex published the trial results in the The Lancet Respiratory Medicine journal. The article was titled “Efficacy and safety of lumacaftor and ivacaftor in patients aged 6–11 years with cystic fibrosis homozygous for F508del-CFTR: a randomised, placebo-controlled phase 3 trial.”
The other Phase 3 trial (NCT02390219) assessed the effectiveness of two Orkambi regimens in patients with CF who had advanced lung disease. These patients also had two copies of the F508del mutation, but were aged 12 or older.
In the 24-week, open-label study, 18 patients received half a dose of Orkambi every 12 hours for two weeks, then a full dose for 22 weeks. Other patients started and stayed with a full dose.
Those who began with half a dose experienced fewer respiratory problems, and the problems were shorter, than those who started with a full dose.
Updates of other clinical trials that Vertex presented at the meeting included the findings that Orkambi improves a measure of lung function known as acute improvement in forced expiratory volume in 1 second, or FEV1, and it reduces the rate of lung function decline over the long term.
“Thousands of patients around the world are benefitting from Kalydeco and Orkambi, which have both shown the ability to modify the progression of CF,” Chodakewitz said. “The data presented at this meeting further demonstrate that treatment with CFTR modulators can deliver early and sustained benefits for eligible patients.”
The U.S. Federal Drug Administration approved Orkambi in September 2016 as a treatment for children aged 6-11 with CF who have two copies of the F508del mutation. Vertex submitted a Marketing Authorization Application extension in Europe for Orkambi in March 2017. It also covers the therapy’s use in children.
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