The US Food and Drug Administration (FDA) has approved Vertex Pharmaceuticals Incorporated's Kalydeco (ivacaftor), the first medicine to treat the underlying cause of cystic fibrosis (CF), a rare, genetic disease.

Kalydeco (kuh-LYE-deh-koh) is approved for people with CF ages 6 and older who have at least one copy of the G551D mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Approximately 1,200 people in the United States, or 4 per cent of those with CF, are believed to have this mutation. Kalydeco was granted approval in approximately three months, making it one of the fastest FDA approvals ever and marking the second approval of a new medicine from Vertex in less than a year. The company has established a financial assistance and patient support programme  to help get Kalydeco to eligible patients for whom it is prescribed. Kalydeco was discovered as part of a collaboration with Cystic Fibrosis Foundation Therapeutics, Inc., the nonprofit drug discovery and development affiliate of the Cystic Fibrosis Foundation.

Vertex is ready to support the introduction of Kalydeco and will begin shipping it to pharmacies in the United States this week.

"More than 13 years ago we set out to change the lives of people with cystic fibrosis by developing new medicines that address the underlying cause of this rare and devastating disease," said Jeffrey Leiden, M.D., Ph.D., Vertex's incoming president and chief executive officer. "Kalydeco represents a major advance in the treatment of cystic fibrosis for people with a specific type of this disease. But our work isn't done. With the ongoing support of doctors, patients and the Cystic Fibrosis Foundation, we're making progress toward our ultimate goal of developing additional medicines to help many more people with cystic fibrosis."

The approval of Kalydeco was based on data from two phase 3 studies of people with CF who have at least one copy of the G551D mutation. Those who were treated with Kalydeco experienced significant and sustained improvements in lung function as well as other disease measures, including weight gain and certain quality of life measurements, compared to those who received placebo. People who took Kalydeco also experienced significantly fewer pulmonary exacerbations, which are periods of worsening in the signs and symptoms of the disease that often require treatment with antibiotics and hospital visits. Fewer people in the Kalydeco treatment groups discontinued treatment due to adverse events than in the placebo groups. The majority of adverse events associated with Kalydeco were mild to moderate. Adverse events commonly observed in those taking Kalydeco included headache, upper respiratory tract infection (common cold), stomach pain and diarrhoea.

"Advances in cystic fibrosis treatment have helped manage symptoms of the disease, however people with cystic fibrosis still have a hard time staying healthy and being active," said Bonnie Ramsey, M.D., director of the Center for Clinical and Translational Research at Seattle Children's Research Institute and principal investigator for one of the phase 3 Kalydeco trials. "Kalydeco is a fundamental shift in the way cystic fibrosis is treated. In people with a specific genetic mutation, Kalydeco helped them breathe more easily, gain weight and generally feel better."

"Together, we're changing the lives of people with cystic fibrosis," said Robert J. Beall, Ph.D., president and CEO of the Cystic Fibrosis Foundation. "We now have a medicine that treats the underlying cause of the disease in people with the G551D mutation. Kalydeco also provides us with a roadmap for exploring additional targeted approaches to treatment for all people with cystic fibrosis."

Cystic fibrosis is a rare, life-threatening genetic disease for which there is no cure. CF is caused by defective or missing CFTR proteins resulting from mutations in the CFTR gene. CFTR proteins act as channels at the cell surface that control the flow of salt and water across the cells. When the defective CFTR protein does not work properly at the cell surface, abnormally thick, sticky mucus builds up in the lungs. The digestive tract and a number of other organs are also affected. Kalydeco, an oral medicine known as a CFTR potentiator, helps the CFTR protein function more normally once it reaches the cell surface. Kalydeco targets the abnormal CFTR protein channels and opens them to allow chloride ions to move into and out of the cell, which helps thin the mucus so it can hydrate and protect the airways, and keeps them from getting clogged and then infected.

Because Kalydeco targets a specific genetic mutation, a person's genotype should be known before this new medicine is prescribed. Genetic testing is widely available and FDA-cleared tests are available for people with CF whose genotype is unknown. According to the 2010 Cystic Fibrosis Foundation's Patient Registry, nearly 92 percent of people with CF have already had their CF mutations identified.

Kalydeco by itself works in a subset of people with CF, but research is ongoing to explore a similar targeted approach using a combination of medicines, including Kalydeco, to treat the most common form of the disease.

Kalydeco is the first treatment to target the underlying cause of CF. The Phase 3 studies evaluated Kalydeco in people with CF ages 6 and older who had at least one copy of the G551D mutation. PERSIST, a Phase 3, open-label, 96-week extension study, is underway to evaluate the long-term safety and durability of treatment with Kalydeco. This ongoing study enrolled people who completed 48 weeks of treatment in either phase 3 study (placebo and Kalydeco treatment groups) and met other eligibility criteria. Kalydeco will be taken as one 150-mg tablet twice daily (every 12 hours).

Vertex retains worldwide rights to develop and commercialize Kalydeco. In October 2011, Vertex submitted a marketing authorization application to the European Medicines Agency (EMA) for Kalydeco and has received agreement from the EMA for accelerated assessment in Europe. The EMA regulatory review is ongoing.