Lumacaftor (VX-809) is an investigational drug developed by the Massachusetts-based pharmaceutical company Vertex for the treatment of patients who suffer from cystic fibrosis (CF) and have the F508del mutation in the CF transmembrane conductance regulator (CFTR).
Currently, lumacaftor is approved by the U.S. FDA as a combined oral treatment for CF in combination with Kalydeco (ivacaftor). Lumacaftor is commercialized by Vertex under the brand name Orkambi, and Kalydeco was approved in the United States in 2012. The lumacaftor/Kalydeco combo was approved by the FDA in July 2015 for patients ages 12 and older, while the use of lumacaftor alone is still being studied by Vertex.
How Lumacaftor Works
Lumacaftor is one of the few compounds approved for patients with cystic fibrosis that targets the underlying causes of the disease, rather than treating the severity of the symptoms. The mechanism of action of lumacaftor is based on the interference with the F508 CFTR. The chronic disease is caused by a mutation in the gene that controls the salt transportation in the cells, resulting in thick, sticky mucus in the respiratory, digestive, and reproductive systems.
To address that genetic defect, lumacaftor helps correct the mutated genes with a novel therapeutic approach. Both lumicaftor and kalydeco work by correcting the misfolded CFTR protein, the root cause of the F508del mutation, which led to the approval of the combined treatment by the FDA. However, while kalydeco alone is also approved by the FDA, the use of lumacftor alone has not yet been approved.
Vertex conducted two studies called TRAFFIC and TRANSPORT to evaluate both lumacaftor and kalydeco, which produced encouraging results as a combined therapy. The combo therapy was able to improve patients’ mucus clearance, which reduces the risk of inflammation in the lungs. However, despite the ability of lumacaftor to improve lung function in combination with kalydeco, the same was not verified in patients administered with only lumacaftor.
Vertex studies demonstrated that being a CFTR corrector, lumacaftor alters the functioning of the protein in patients with two copies of the F508del gene. By affecting the damage in the gene, it helps restore the normal function, increasing the amount of functional protein at the cell surface. Lumacaftor is able to both address the processing and trafficking malfunction of the protein, while it enables the transport of salt.
More Information About Lumacaftor
According to the Cystic Fibrosis Foundation and the UK CF Registry, the leading cause for the development of CF is inheriting two copies of the F508del mutation, and about half of the CF patients in the U.S. and U.K. have this mutation.
The combination therapy of 200 mg of lumacaftor with 125 mg of Kalydeco may be able to treat an estimated 8,500 patients age 12 and older in the United States. The studies in question received significant clinical, scientific, and funding support from the Cystic Fibrosis Foundation.
There is currently no cure for this rare, genetic, and life-threatening disease that affects about 75,000 patients in North America, Europe, and Australia. In the U.S. alone, approximately 30,000 people are diagnosed with CF; the estimated age of survival for patients is currently between 34 and 47 years. Although there is encouraging news, such as the results with therapies that address the F508del mutation, there are more than 1,800 known mutations in the cystic fibrosis gene.