New cystic fibrosis drug tested

Monday December 20 2010

A new drug “helps clear mucus in cystic fibrosis patients”, BBC News has reported. The website says that a study in children and young adults found that the drug, denufosol, helped keep airways moist and clear of mucus.

In cystic fibrosis the lungs, digestive system and other organs become clogged with a thick, sticky mucus that can lead to infections and serious complications. This 24-week trial randomly assigned 252 people either a placebo solution or inhaled denufosol, which is designed to target the mechanisms that produce the troublesome mucus. After the trial the denufosol group saw a 48ml improvement in the volume of air that could be forcibly exhaled in one second. This improvement of 2% was significantly better than the 3ml improvement in the placebo group. The drug also had a good safety profile.

This initial trial suggests an application for the drug in young people with early-stage cystic fibrosis displaying milder lung impairment. Denufosol is currently being tested in a longer trial in a larger group, which should give a clearer indication of the drug’s potential. The UK's Cystic Fibrosis Trust considers the findings of this early trial to be “promising”.

Where did the story come from?

This study was carried out in the US by researchers from the University of Colorado, Stanford University, Saint Louis University, SUNY Upstate Medical University, the University of Washington and Inspire Pharmaceuticals, which also provided funding for the research.

The study was published in the peer-reviewed American Journal of Respiratory and Critical Care Medicine.

BBC News has accurately reflected the findings of this research.

What kind of research was this?

Cystic fibrosis (CF) is a genetic condition that causes a number of health problems, but primarily progressive damage to the lungs caused by a build-up of thick, sticky mucus within the body. People with CF produce this mucus within their bodies due to an inherited genetic mutation that changes the way that their cells handle fluids and salts. Sufferers usually need physiotherapy to remove the mucus from their lungs, and often need antibiotics for chest infections.

As well as clogging and coating the lungs, this mucus can build up in a number of other organs over time, leading to problems such as diabetes, inability to absorb nutrients from food and infertility in male sufferers. Life expectancy is typically reduced to middle age. Cystic fibrosis is one of the most common inherited diseases, affecting around 8,500 people in the UK.

The gene that leads to CF is recessive, meaning that you must inherit two copies (one from each parent) in order to have the condition. However, one person in 25 is a carrier of the CF gene, which means they are not affected by the disease but that their offspring may be if their partner also carries a CF gene. If two carriers have a child there will be:

  • a one in four chance that their child will inherit two copies of the recessive gene and therefore have cystic fibrosis
  • a one in two chance that their child will only inherit a single CF gene and therefore be unaffected but a carrier
  • a one in four chance that their child won’t inherit any CF genes and therefore won’t be a carrier or have cystic fibrosis

Current therapies predominantly address the complications of CF, such as using physiotherapy and inhalers to try to clear mucus and improve breathing. However, the root of the problem lies with the CF mutation, which affects a gene that controls ion transport channels in the body. The current research investigated a new drug called denufosol, which is designed to work directly on the ion channels that produce mucus, rather than trying to alleviate the symptoms that the mucus causes. As this drug is designed to target the underlying biological processes of the disease it is hoped that it could potentially modify the course of the disease, particularly if administered at an early stage.

The current study was the first randomised controlled trial designed to investigate the safety and effectiveness of this drug in people with early CF who had not yet developed significant impairment of their lung function.

What did the research involve?

The research involved 352 children or young adults, aged at least five years, who had CF but normal or minimally-impaired lung function. This was confirmed using a test of ‘forced expiratory volume’ at one second (FEV1, which is the volume of air that can be forcefully breathed out in the first second of exhalation). Participants were required to display an FEV1 score of at least 75% of that expected for a person of their age, sex and height. Participants were on stable medications and had had no illnesses within the past four weeks. They were randomly allocated 24 weeks’ treatment with either inhaled denufosol (60mg three times daily) or a placebo medication (inhaled saline).

Safety was assessed through adverse event reporting, physical examination, chest X-rays and other clinical and laboratory assessment. The main efficacy outcome was change in FEV1 performance at 24 weeks.

What were the basic results?

The study was completed by 89% of those randomised. At 24 weeks there was a borderline significant increase in FEV1 in the denufosol group (0.048L increase) compared with the placebo group (0.003L increase; difference between groups p=0.047).

The groups showed no significant differences in other, secondary measures of lung function: forced vital capacity (volume of air during maximal exhalation after maximal inhalation), forced expiratory flow (flow of air during the middle phase of exhalation) and no difference in the rate of exacerbation of lung function (defined by meeting at least four of a set of 12 clinical signs and symptoms).

Denufosol was well-tolerated, with an adverse event profile similar to the inactive placebo drug. Nearly all patients in both groups reported at least one adverse effect during the study, most commonly cough. Sinusitis, runny nose and headache were reported more often in the placebo group. Withdrawals due to adverse effects were rare, and occurred with a 1-3% frequency across both groups.

How did the researchers interpret the results?

The researcher concluded that the results of this double-blind, placebo-controlled randomised controlled trial demonstrate that the ion channel regulator denufosol has efficacy and safety profiles suitable for early intervention in people with cystic fibrosis who have little or no lung function impairment.


This was a well-conducted randomised controlled trial with strengths including its relatively large size and high completion rates in both denufosol and placebo groups. Denufosol had a good safety profile, and at 24 weeks it gave an improvement in the primary outcome of FEV1 (the volume of air that can be forcefully breathed out in the first second of exhalation).

Though this trial has promising results, it should be remembered that:

  • After denufosol treatment, FEV1 performance was improved by 2% compared with that at the start of the study (a 48ml increase). Though better than the 3ml improvement in those receiving the saline control solution the difference between the groups only just reached statistical significance (p=0.047 [significance is <0.05]).
  • This initial trial did not demonstrate any improvements in other measures of lung function or on the rate of infections, which are a recurring problem among people with CF.
  • All study members had early-stage disease with no or minimal impairment of lung function (average FEV1 92% of what would be expected for a person of their age, sex and height). Therefore, the findings cannot be extrapolated to children and young adults with CF who have greater impairment or to older groups with mild CF impairment.
  • Further assessment of safety and efficacy will be required in a larger sample of people with CF treated over a longer time period. Such a study is currently ongoing.

Cystic fibrosis is an incurable condition that can cause a number of major health problems. While current treatments tend to focus on management of the symptoms of CF, it is encouraging to see the development of drugs designed to target the root biological problems that lie behind the condition. That said, this well-conducted research is only the first trial of denufosol, and further, larger trials will now be needed to give a better indication of its safety and efficacy over the longer term, and in sufferers who have different levels of lung function.

Analysis by Bazian
Edited by NHS Choices