How many people does cystic fibrosis affect and why is it a life-shortening illness?
Cystic fibrosis is a rare, life-shortening genetic disease for which there is no cure. It affects more than 75,000 people worldwide.
In CF, thick, sticky mucus blocks the passages in many organs, leading to a variety of symptoms. In particular, mucus builds up and clogs airways in the lungs making it easier for bacteria to grow.
Repeated infections and chronic inflammation can lead to lung disease, which damages the lungs and is a leading cause of death in people with CF.
Globally, the average age of death for people with CF is in a person’s mid-20s.
Please can you outline what is known about the causes of cystic fibrosis?
Cystic fibrosis is caused by a defective or missing cystic fibrosis transmembrane conductance regulator (CFTR) protein, which results from mutations in the CFTR gene.
Children must inherit two defective CFTR genes — one from each parent — to have CF. Each child born of two parents who carry the defective CFTR gene has a one-in-four chance of having CF.
There are more than 1,900 known mutations in the CFTR gene, and some of these mutations, which can be determined by a genetic, or genotyping test, lead to CF by creating non-working or too few CFTR protein at the cell surface.
The CFTR protein is essential to regulating the flow of salt and water into and out of the cell in a number of organs, including the lungs.
When the protein does not work properly or does not exist, abnormally thick, sticky mucus accumulates and can cause chronic lung infections and progressive lung damage.
Vertex has been working to develop new medicines to treat cystic fibrosis for over 15 years. How have treatments progressed over this time?
In 1998, Vertex set out to change the way CF was treated by targeting the underlying cause of the disease – the protein defect. At the time, much of the research interest and investment was focused on gene replacement therapy.
Nearly all CF medicines that have been developed to-date treat the symptoms and/or the complications of the disease. Kalydeco (ivacaftor) is the first and only medicine to treat the underlying cause of cystic fibrosis and has fundamentally changed the way the disease is treated in people with the G551D mutation.
The goal of Vertex’s CF program has always been to develop new medicines that treat the underlying cause of the disease in order to help as many people with this rare but devastating disease as possible.
We’re continuing to work toward this goal by investing significantly in research and development efforts that are exploring similar targeted approaches to help many more people with the disease.
Our efforts include multiple studies designed to evaluate whether additional people with CF my benefit from treatment with ivacaftor alone, as well as studies of ivacaftor in combination with lumacaftor in people with the most common CF mutation, F508del.
What is the G551D mutation and how many cystic fibrosis patients are thought to carry this specific genetic mutation?
The G551D mutation is one of a number of “gating mutations”, so called because, although the CFTR protein reaches the cell surface, it does not open (gate) properly to allow a healthy exchange of salt and water into and out of the cell.
In people with the G551D mutation, Kalydeco helps the defective CFTR protein function more normally. More than 2,000 people worldwide have the G551D mutation.
Could you please outline the two global Phase 3 studies of people with cystic fibrosis and at least one copy of the G551D mutation?
In Phase 3 clinical studies, Kalydeco demonstrated unprecedented improvements in outcomes for people with CF who have the G551D mutation.
Those who received Kalydeco experienced significant and sustained improvements in lung function as well as a variety of other disease measures, including weight gain and certain quality of life measurements, compared to those receiving placebo.
In addition, adolescents and adults who received KALYDECO were 55 per cent less likely to have pulmonary exacerbations, or periods of worsening respiratory signs and symptoms that often require treatment with antibiotics and hospital in-patient visits, than those who received placebo.
These two Phase 3 studies, STRIVE and ENVISION, involved 161 people with CF ages 12 and older and 52 children with CF ages 6 to 11, respectively, who have at least one copy of the G551D mutation.
What excites you most about the results of these studies?
In Phase 3 trials, treating the underlying cause of CF with Kalydeco led to clinical improvements that were far beyond expectations.
Data from these studies of Kalydeco in people with the G551D mutation demonstrate that treating the underlying cause of CF significantly improves outcomes for people with the disease.
These data open the door to an entirely new approach to the treatment of CF and also offer significant hope that a similar approach to treatment may help others living with the disease.
What hurdles still need to be overcome in order to develop further treatments for cystic fibrosis?
Kalydeco represents an exciting new beginning in the treatment of CF; it has fundamentally changed the way the disease is treated in people with a specific mutation and has also shown what is possible by treating the underlying cause of the disease.
However, there is a lot more work to be done to develop similar targeted treatments people with other mutations in the CFTR gene.
What are Vertex’s plans for the future?
Sixteen years ago Vertex set out to change the lives of people with CF by developing new medicines that treat the underlying cause of this rare and devastating disease.
While Kalydeco represents a major advance in the treatment of cystic fibrosis for people with a specific type of this disease, our work isn't done.
With the ongoing support of doctors, patients and the CF community, we're making progress toward our ultimate goal of developing additional medicines to help many more people with cystic fibrosis.
Where can readers find more information?
To know more about CF, readers can get in touch with Cystic Fibrosis Australia who can provide information on the disease, diagnosis, treatment and care, and advice on living with CF or caring for a loved one with CF. For more information about Vertex Pharmaceuticals, please visit: www.vrtx.com.
About Simon Bedson
Simon Bedson, Senior Vice President and International General Manager at Vertex, has three decades of pharmaceutical and biotech industry experience. He joined Vertex in 2011 to lead the company’s global expansion.
Mr. Bedson oversees global commercial activities outside of North America, which have included the establishment of the company’s first international headquarters in Switzerland as well as commercial offices and operations in Australia, the UK and Republic of Ireland, France, Germany, Benelux, Spain and Italy.
Mr. Bedson joined Vertex from Gilead, where he led the creation of country operations and leadership in nine affiliate markets over a three-year period. Prior to that, Mr. Bedson spent 10 years at Amgen, including four at the company’s U.S. headquarters, in a variety of leadership roles.