Orkambi (lumacaftor 200 mg/ivacaftor 125 mg) has now been approved by the FDA to treat cystic fibrosis (CF) in patients 12 years and older, who have the F508del mutation, which causes the production of an abnormal protein that disrupts how water and chloride are transported in the body. Having two copies of this mutation (one inherited from each parent) is the leading cause of Cystic Fibrosis (CF).
Cystic Fibrosis is a serious genetic disorder that results in the formation of thick mucus that builds up in the lungs, digestive tract and other parts of the body leading to severe respiratory and digestive problems, as well as other complications such as infections and diabetes. It is now estimated that 30,000 people in the United States now suffer from the disease, now considered to be “the most common fatal genetic disease in Caucasians.” The F508del mutation is the most common cause of CF. People who have two copies of the F508del mutation, one inherited from each parent, account for approximately half of the CF population in the US.
“The FDA encourages manufacturers to develop new and innovative treatments for serious rare diseases like cystic fibrosis,” said John Jenkins, M.D., director of the Office of New Drugs, Center for Drug Evaluation and Research. “This new approval significantly broadens the availability of targeted treatments for the specific defects that cause cystic fibrosis.”
Orkambi received FDA’s breakthrough therapy designation because the sponsor demonstrated through preliminary clinical evidence that the drug may offer a substantial improvement over available therapies. The FDA also reviewed Orkambi under the priority review program. A priority review is conducted over six months, or less, instead of the standard 10 months, and is employed for drugs that may offer significant improvement in safety or effectiveness in treatment over available therapy in a serious disease or condition.
The safety and efficacy of Orkambi was studied in two double-blind, placebo-controlled clinical trials of 1,108 participants with CF who were 12 years and older with the F508del mutation. In both studies, participants with CF who took Orkambi, two pills taken every 12 hours, demonstrated improved lung function compared to those who took placebo.
The efficacy and safety of Orkambi, however, have not been established in patients with CF other than those with the F508del mutation. If a patient’s genotype is unknown, an FDA cleared CF mutation test should be used to detect the presence of the F508del mutation on both alleles of the CFTR gene.
The most common side effects of the drug include shortness of breath, upper respiratory tract infection, nausea, diarrhea, and rash. Women who took Orkambi also had increased menstrual abnormalities such as increased bleeding.