The US Food and Drug Administration (FDA) has approved Vertex Pharmaceuticals’ drug for cystic fibrosis (CF) directed at treating the cause of the disease in people who have two copies of a specific mutation. Orkambi (lumacaftor 200 mg/ivacaftor 125 mg) was approved to treat 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 CF, according to the FDA.

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. In addition, the FDA granted Orkambi orphan drug designation because it treats cystic fibrosis, a rare disease. Orphan drug designation provides financial incentives, like clinical trial tax credits, user fee waivers, and eligibility for market exclusivity to promote rare disease drug development.

CF 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. CF is caused by defective or missing cystic fibrosis transmembrane conductance regulatory (CFTR) proteins resulting from mutations in the CFTR gene. The defective or missing proteins result in poor flow of salt and water into or out of the cell in a number of organs, including the lungs. In people with two copies of the F508del mutation, the CFTR protein is not processed and trafficked normally within the cell, resulting in little to no CFTR protein at the cell surface. Patients with two copies of the F508del mutation are identified by a simple genetic test. Orkambi is a combination of lumacaftor, which is designed to increase the amount of mature protein at the cell surface by targeting the processing and trafficking defect of the F508del CFTR protein, and ivacaftor, which is designed to enhance the function of the CFTR protein once it reaches the cell surface.

Source: FDA and Vertex Pharmaceuticals