On July 2, the Food and Drug Administration (FDA) approved the first drug for cystic fibrosis (CF), which is focused on treating the cause of the disease in individual who have two copies of a specific mutation. Orkambi (lumacaftor 200 mg plus ivacaftor 125 mg) is now approved to treat CF) in patients 12 years and older who have the F508del mutation; this mutation 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 CF. Orkambi is manufactured by Vertex Pharmaceuticals Inc., Boston, Massachusetts.
“The FDA encourages manufacturers to develop new and innovative treatments for serious rare diseases like cystic fibrosis,” explained John Jenkins, M.D., director of the Office of New Drugs, Center for Drug Evaluation and Research. He added, “Today’s approval significantly broadens the availability of targeted treatments for the specific defects that cause cystic fibrosis.”
The FDA announcement noted that Orkambi received FDA’s breakthrough therapy designation because the manufacturer demonstrated via preliminary clinical evidence that the medication may offer a substantial improvement over available therapies. The FDA also reviewed Orkambi under its priority review program. This type of review is conducted over six months, or less, instead of the standard 10 months; furthermore, 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 FDA also granted Orkambi an orphan drug designation because it treats cystic fibrosis, which is classified as a rare disease. Orphan drug designation provides financial incentives, such as clinical trial tax credits, user fee waivers, and eligibility for market exclusivity to promote rare disease drug development. The safety and effectiveness of Orkambi was assessed in two double-blind, placebo-controlled clinical trials of 1,108 participants with CF who were 12 years and older with the F508del mutation. Double blinding denotes that neither the prescriber nor the subject is aware of whether the drug or placebo is given. In both studies, participants with CF who took Orkambi, two pills taken every 12 hours, were found to have improved lung function compared to those who took placebo.
The FDA notes that the safety and effectiveness of Orkambi have not been established in patients with CF other than those with the F508del mutation. If a patient’s genotype (genetic code) is unknown, an FDA-cleared CF mutation test should be used to detect the presence of the F508del mutation on both CFTR genes. The most common side effects of Orkambi include shortness of breath, upper respiratory tract infection, nausea, diarrhea, and rash. Women who took the medication also had increased menstrual abnormalities such as increased bleeding.
According to the Cystic Fibrosis Foundation, CF is a life-threatening genetic disease that primarily affects the lungs and digestive system. An estimated 30,000 children and adults in the United States (70,000 worldwide) have CF. Facts about CF in the US:
- About 1,000 new cases of CF are diagnosed each year
- More than 75% of individuals with CF are diagnosed by age 2
- Nearly half of the CF population is age 18 or older
In individuals with CF, a defective gene and its protein product cause the body to produce unusually thick, sticky mucus that: clogs the lungs and leads to life-threatening lung infections; and obstructs the pancreas and stops natural enzymes from helping the body break down food and absorb vital nutrients.
In the 1950s, few children with CF lived to attend elementary school. Since then, tremendous progress in understanding and treating CF has led to dramatic improvements in the length and quality of life for those with CF. Many people with the disease can now expect to live into their 30s, 40s and beyond.
Individuals with CF can have a variety of symptoms, including:
- Very salty-tasting skin
- Persistent coughing, at times with phlegm
- Frequent lung infections
- Wheezing or shortness of breath
- Poor growth and slow weight gain, despite a good appetite
- Frequent greasy, bulky stools or difficulty in bowel movements