Cystic fibrosis drug double-up does well in trial

A combination of two gene-targeting drugs significantly increases the lung function of cystic fibrosis (CF) patients, clinical trials show.

Although the results appear to be 'at the low end of what some doctors would consider meaningful', according to The New York Times, they have sparked a flurry of interest from investors in Vertex Pharmaceuticals, the company behind the drugs.

The drugs are not a cure for CF, but rather aim to improve patient quality of life. Speaking during a webcast, Vertex chief executive Dr Jeffrey Leiden said: 'For these patients every improvement that they have in lung function, and every day they don't spend in the hospital, and every pound they gain is meaningful to them and their families. And that's why we're so pleased with the results'.

CF is an genetic condition in which the lungs and digestive system become clogged with thick, sticky mucus. A few decades ago, most patients would die from complications before adulthood but now, according to The Cystic Fibrosis Trust, 'more than half of the CF population in the UK will live past 41'. Over 10,000 people have CF in the UK.

CF is caused by a malfunctioning protein, called CFTR. This protein can be inactivated by mutation in several genes, which means there are multiple genetic targets for drug developers. One of the drugs in the combination, ivacaftor (marketed as Kalydeco), has been approved since 2012, but is only effective for the 2,200 patients worldwide with the rare G551D mutation.

By combining ivacaftor with another Vertex drug, lumacaftor, the goal is to extend treatment to half of all CF patients who possess two copies of the F508del mutation.

The average lung capacity improvement of the F508del patients was only a third of the ten percent improvement experienced by G551D patients taking Kalydeco. But the 1,100 patients in the two phase III clinical trials gained an average of 1.6 pounds in weight, and were less likely to catch infections resulting in hospitalisation.

'On average, people with CF who have two copies of the F508del mutation lose nearly two percent of their lung function each year, underscoring the urgent need for new medicines', said Dr Bonnie Ramsey, professor at the University of Washington School of Medicine and lead investigator on one of the trials.

Discussing the lower-than-ideal increase in lung capacity with The New York Times, Professor Ramsey said: 'Would I have rather seen six, seven percent? Of course'. But maintained that the results represented a 'very positive step forward'.

Some questions remain about the study: why the drugs' effect was not dose-dependent; and why, paradoxically, shortness of breath was noted as a side effect.

Although the data have not yet been analysed by the Food and Drug Administration, Vertex's stock price has risen sharply - a sign that industry investors are confident the drug combination will soon be available commercially.

In a statement included on Vertex's press release, Dr Robert Beall, president and CEO of the Cystic Fibrosis Foundation in the USA said the results 'mark an exciting day for the CF community and validate our more than 30-year commitment to develop medicines that target the underlying basic defect of CF for all people with this devastating disease'.

According to Forbes magazine, the studies also serve to validate a novel research technique developed by Dr Fred Van Goor, the head of Vertex's research programme - a cell culture assay nicknamed the 'lung-in-a-dish'.