More patients with cystic fibrosis could benefit from treatment with Vertex Pharmaceuticals' disease-modifying drug Kalydeco if it is combined with a second drug, according to new phase III data.
Vertex won approval for Kalydeco in 2012 as a treatment for cystic fibrosis patients with a genetic mutation known as G551D in the CF transmembrane conductance regulator (CFTR) gene, becoming the first medicine to be approved that addresses the underlying causes of the disease rather than its symptoms.
Now, two pivotal trials show that combining Kalydeco with a second drug - called lumacaftor (formerly VX-809) - is effective in treating cystic fibrosis patients with another CFTR mutation called F508del.
This is the most common cause of the disease, affecting around 22,000 people in North America, Europe and Australia or around 60 per cent of all patients. The G551D mutation accounts for around 4 per cent of cases.
The CFTR protein regulates salt and water transport in the body and when impaired it causes a accumulation of mucus in a number of organs, but particularly the lungs which become clogged, lose their ability to remain sterile and are gradually destroyed by repeated infections.
Prior to the approval of Kalydeco, the only pharmacological treatment options were antibiotics to combat infections and enzyme therapy to try to thin down the mucus.
In trials involving 1,106 patients with the F508del mutation, the combination of Kalydeco and lumacaftor achieved significant improvements in lung function, measured using a scale known as percent predicted forced expiratory volume in one second (ppFEV1).
Vertex' new therapy achieved improvements of 2.6 to 4 per cent on this measure in absolute terms, and patients receiving the therapy outperformed those on placebo by 4.3 to 6.7 per cent over the 24-week period.
Patients on the combination also had significantly fewer pulmonary exacerbations than placebo - down by around a third - and showed improvements on general health measures such as body mass index (BMI).
The results were applauded by the Cystic Fibrosis Foundation in the US, which provided $75m in funding for the research. The organisation's chief executive, Robert Beal, said: "many people with cystic fibrosis and their families have been eagerly awaiting these results, and we are thrilled with the outcome."
The CFF notes that repairing the F508del mutation is particularly challenging as a series of problems prevent the CFTR protein achieving the correct shape and reaching the surface of the cell.
Vertex said it will move quickly to file the combination in the US and Europe, raising the prospect of approval in 2015 and additional growth momentum to Kalydeco, which pulled in revenues of around $370m last year.
Analysts have cast a critical eye over the data, however, and some have expressed concerns that the lung function benefit seems reduced compared to a phase II trial of the combination and a ppFEV1 improvement of around 3 per cent could not be clinically meaningful to patients.
Vertex suggests that extending treatment beyond 24 weeks could have a meaningful impact, not only in terms of lung function but also in reduced exacerbations, lung damage and hospitalisations.