First drug to treat underlying cause of cystic fibrosis approved in the US
This article was originally published in Scrip
The US FDA has approved Vertex Pharmaceuticals' Kalydeco (ivacaftor; previously known as VX-770) as the first medicine to treat the underlying cause of cystic fibrosis (CF).
"Kalydeco is an excellent example of the promise of personalised medicine – targeted drugs that treat patients with a specific genetic makeup," said FDA Commissioner Dr Margaret Hamburg in a statement.
The product is approved for people aged six and older with CF who have at least one copy of the G551D mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Currently available medicines treat the symptoms and some of the complications of the disease, but not the underlying cause of CF.
According to Vertex, 1,200 people in the US, or 4% of CF sufferers, are believed to have this mutation. Kalydeco was granted approval in about three months, "making it one of the fastest FDA approvals ever", noted Vertex, and marking the second approval of a new medicine from Vertex in less than a year. It follows the approval of Incivek (telaprevir) for hepatitis C last year. Vertex filed Kalydeco last October (scripintelligence.com, 20 October 2011).
Kalydeco will cost a hefty $294,000 per patient each year, the company said in a conference call. Vertex has established a financial assistance and patient support programme to help get the product to patients. It will begin shipping the new drug to pharmacies in the US this week.
The drug was discovered as part of a collaboration with Cystic Fibrosis Foundation Therapeutics, the non-profit drug discovery and development affiliate of the Cystic Fibrosis Foundation. The Foundation put $75 million of investment into the drug, and will get undisclosed royalties on sales.
The approval of Kalydeco was based on data from two Phase III studies of people with CF who have at least one copy of the G551D mutation, the STRIVE and ENVISION studies. In some people with CF, CFTR proteins are present at the cell surface but do not function properly – a dysfunction known as a gating defect, the most common of which is the G551D mutation. Kalydeco is designed to keep the CFTR channels at the cell surface open longer to improve the transport of chloride ions across the cell membrane in people who have gating mutations.
Those 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.
Vertex was quick to note that while Kalydeco works by itself in a subset of people with CF, "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's approval application also included data from Vertex's Phase II DISCOVER study, which evaluated the drug in patients with two copies of the F508del mutation, the most common CFTR mutation.
Vertex retains worldwide rights to develop and commercialise Kalydeco. The company submitted a marketing authorisation application to the European Medicines Agency for Kalydeco in October last year and has received agreement from the EMA for accelerated assessment. The EMA regulatory review is ongoing.