Vertex Pharmaceuticals Incorporated, a global biotechnology company, announced that the US Food and Drug Administration (FDA) has accepted for review a supplemental New Drug Application (sNDA) for the use of Orkambi (lumacaftor/ivacaftor) in people with cystic fibrosis (CF) ages 6 to 11 who have two copies of the F508del mutation. The FDA granted Vertex's request for Priority Review of this sNDA, and a target review date of September 30, 2016 was set under the Prescription Drug User Fee Act (PDUFA).
"As complications related to CF can occur early in life, we believe it is important to begin treatment as early as possible and this supplemental New Drug Application for approval of Orkambi in children as young as six is an important step in that direction," said Jeffrey Chodakewitz, M.D., executive vice president and chief medical officer at Vertex. "This submission demonstrates Vertex's continued progress toward our goal of developing medicines for all people with CF."
The sNDA is based on data from an open label phase 3 clinical safety study of Orkambi. Data from this study will be presented at the 39th European Cystic Fibrosis Society conference being held June 8 to 11 in Basel, Switzerland.
To support potential approval in the European Union, a six-month phase 3 efficacy study of children ages 6 to 11 is ongoing. Vertex recently completed enrollment in this study and, pending data from the study, plans to submit a Marketing Authorization Application (MAA) variation in the European Union in the first half of 2017 for children ages 6 to 11 who have two copies of the F508del mutation. The primary endpoint of this efficacy study is the absolute change in lung clearance index (LCI). There are approximately 3,400 children ages 6 to 11 who have two copies of the F508del mutation in the European Union.
Cystic fibrosis is a rare genetic disease that is caused by defective or missing cystic fibrosis transmembrane conductance regulator (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 easily 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. Orkambi is taken every 12 hours - once in the morning and once in the evening with fat-containing food.
The most common side effects of Orkambi include shortness of breath and/or chest tightness; upper respiratory tract infection (common cold), including sore throat, stuffy or runny nose; gastrointestinal symptoms including nausea, diarrhea, or gas; rash; fatigue; flu or flu-like symptoms; increase in muscle enzyme levels; and irregular, missed, or abnormal menstrual periods and heavier bleeding.
Cystic fibrosis is a rare, life-threatening genetic disease affecting approximately 75,000 people in North America, Europe and Australia.
CF is caused by a defective or missing CFTR protein resulting from mutations in the CFTR gene. Children must inherit two defective CFTR genes — one from each parent — to have CF. There are approximately 2,000 known mutations in the CFTR gene. Some of these mutations, which can be determined by a genetic test, lead to CF by creating defective or too few CFTR proteins at the cell surface. The defective or missing CFTR protein results in poor flow of salt and water into or out of the cell in a number of organs, including the lungs. This leads to the buildup of abnormally thick, sticky mucus that can cause chronic lung infections and progressive lung damage in many patients that eventually leads to death. The median predicted age of survival for a person born today with CF in the United States is 39 years, but the median age of death is 29 years.