The US Food and Drug Administration (FDA) has granted approval to Vertex Pharmaceuticals' Orkambi (lumacaftor/ivacaftor), the first medicine to treat the underlying cause of cystic fibrosis (CF) in people aged 12 years and older with two copies of the F508del mutation. It is only indicated for these patients, who can be identified with a genetic test.

Cystic fibrosis is a rare, life-threatening genetic disease. People with two copies of the F508del mutation represent the largest group of people with CF. Of the 30,000 people in the United States with CF, approximately 8,500 aged 12 years and older have two copies of the F508del mutation. Orkambi will be available for shipment to specialty pharmacies in the United States within days.

"Today is a remarkable day for science, medicine and the CF community," said Jeffrey Leiden, M.D., Ph.D., Vertex's chairman, president and chief executive officer. "More than 15 years ago, our scientists set out to discover and develop medicines to treat the underlying cause of cystic fibrosis. Today, the approval of Orkambi represents a fundamental change in the treatment of the most common form of CF, marking significant progress for us and for the entire CF community. While we celebrate this important step forward, we also recognise that two out of three patients in the US still do not have a medicine to treat the underlying cause of their disease. We share their urgency and are committed to continuing our significant investment in research and development to discover new medicines for them and to improve upon what we offer patients today."

The approval of Orkambi was based on data from two phase 3 studies (TRAFFIC and TRANSPORT) that enrolled more than 1,100 people with CF ages 12 and older with two copies of the F508del mutation. Patients treated with Orkambi  experienced statistically significant improvements in lung function. Patients also experienced reductions in pulmonary exacerbations and improvements in body mass index (BMI). The most common adverse events included shortness of breath and/or chest tightness, upper respiratory tract infection (common cold) and gastrointestinal symptoms (including nausea, diarrhea, or gas).

Vertex continues to invest in CF research and development with the goal of treating the vast majority of people with the disease and enhancing the benefit for those we treat. Multiple phase 2 and phase 3 clinical studies are in progress and Vertex has an ongoing research programme focused on discovering new CF medicines.

"In 1998, Vertex and the CF Foundation embarked on a scientific challenge that many believed would be impossible - to discover medicines that treat the cause of CF," said Robert J. Beall, Ph.D., president and chief executive officer of the Cystic Fibrosis Foundation. "Today's approval is a milestone for the CF community. We congratulate Vertex for their success in developing new CF medicines and are pleased with their continuing commitment to help all eligible patients get access to these medicines."

Cystic fibrosis is a rare genetic disease that 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 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.

Worsening of liver function, including hepatic encephalopathy, in patients with advanced liver disease has been reported in some patients with CF while receiving Orkambi. Serious adverse reactions related to elevated transaminases have been reported in patients with CF receiving Orkambi, in some instances, associated with concomitant elevations in total serum bilirubin. Respiratory events (e.g., chest discomfort, shortness of breath, and chest tightness) were observed more commonly in patients during initiation of Orkambi compared to those who received placebo. Clinical experience in patients with percent predicted FEV1 < 40 is limited, and additional monitoring of these patients is recommended during initiation of therapy.

Outside of the US, Vertex has submitted Orkambi for regulatory approval in the European Union, Australia and Canada. A decision by the European Medicines Agency (EMA) is anticipated by the end of 2015. Reviews by Health Canada and Australia's Therapeutic Goods Administration (TGA) are also ongoing.