A pioneering drug has drastically improved the lung function of people with a certain type of cystic fibrosis. It is the first to target the cause, not the symptoms, of the world鈥檚 most common hereditary lung disease, and could be combined with a second new drug to improve the lives of thousands around the world.
Peter Mueller, chief scientific officer for in Cambridge, Massachusetts, and colleagues gave the drug, called , or a placebo to 161 people with cystic fibrosis for a year.
At the outset, most participants had just 60 per cent as much lung function as that of a healthy person. At the end of the trial, those who received VX-770 had an average improvement of almost 20 per cent in their lung function; the lung function of those who received the placebo did not change.
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鈥淭hese data exceeded our expectations,鈥� said Mueller, announcing the results yesterday.
Root of the problem
No other treatments for cystic fibrosis have caused such dramatic improvements, probably because they alleviate symptoms rather than attacking the main cause 鈥� a defective protein in lung cells called the Cystic Fibrosis Transmembrane Regulator, or CFTR, discovered in 1989. VX-770 is the first of a new generation of drugs that attack and correct the protein.
In healthy people, CFTR proteins form channels in the surface membrane of lung and other cells; these channels shuttle chloride ions in and out of the cell. When they fail, the lungs clog up with mucus, making it difficult for people to breathe and making them vulnerable to infections.
VX-770 corrects the channels in people with a certain form of cystic fibrosis who make a faulty form of the protein channel which reaches the cell surface but is always closed. The mechanism isn鈥檛 yet fully understood, but the drug somehow makes the channels open so that they work normally, says at Queen鈥檚 University, Belfast, UK, the principal investigator for the European arm of the trial. 鈥淚t means you have normal regulation of the airway surface liquid, so instead of accumulating mucus, it gets cleared away,鈥� he says.
Additional results from the trial provide evidence that the drug is performing this role. One of the signs of the failing cell membrane channels is a huge accumulation of chloride in sweat, so sweat from people with cystic fibrosis usually has three times the usual concentration of chloride. Chloride concentrations halved in the sweat of participants receiving the drug, bringing them much closer to those seen in healthy people.
Other benefits included 55 per cent fewer 鈥減ulmonary exacerbations鈥� 鈥� deteriorations in symptoms that require antibiotic treatment 鈥� compared with participants receiving the placebo. On average, people receiving the drug also gained around 3聽kilograms, suggesting that the disease鈥檚 usual effects on digestion had eased.
Big news
鈥淭his is a champagne moment for the cystic fibrosis community,鈥� says Elborn at Queen鈥檚 University, Belfast, UK, the principal investigator for the European arm of the trial.
鈥淚t鈥檚 pretty exciting,鈥� said a spokeswoman for the UK鈥檚 . 鈥淚t鈥檚 very big news.鈥�
Announcing the results yesterday, Vertex said it hoped to apply within two or three months to get the drug approved both in the US and Europe. The company developed the drug with support from the US .
Double game
One drawback is that only 5聽per cent of people with cystic fibrosis have the specific mutation that the drug corrects, around 5000 patients worldwide.
But Elborn says there is hope for the rest in the shape of a second drug under development, called VX-809, which could potentially correct a mutation affecting 75 per cent of people with cystic fibrosis.
Those with this mutation make the CFTR protein but fail to deliver it to the cell surface. In experiments on lung cells in culture, Vertex has shown that the new drug successfully brings the protein to the surface.
The key could be to combine the two drugs, with one able to raise the protein to the surface if it鈥檚 not already there, and the other able to prise it open if it remains closed.
The company said yesterday that a small trial of the combination is already under way, and results are expected within months.
