Breathing out BURGER/PHANIE/SCIENCE PHOTO LIBRARY

A drug for cystic fibrosis has improved lung function in children under the age of 12, raising hopes that the life-threatening lung damage caused by the genetic disease can be halted or even reversed.

“It’s a major step forward,” comments Nick Medhurst, head of policy at the UK charity, the Cystic Fibrosis Trust. “What these results show is that it can prevent irreversible damage.”

Since the CFTR gene was discovered in 1989 researchers have tried to develop drugs that directly target the faulty protein it makes in those who have the disease, with some success. Kalydeco helps cells make a correct version of the CFTR protein and has been available since 2012, but it only works for CFTR mutations present in 5 per cent of people with the condition.


By combining Kalydeco with another drug called lumacaftor to create a single medicine called Orkambi, clinicians have since targeted the most common CFTR mutation and extended treatment options to half of all people with cystic fibrosis. Orkambi has been approved in the US, EU and other countries, and has been shown to reduce the number of lung infections people with cystic fibrosis get. However it is not available on the NHS in the UK, because the body NICE – which assesses the cost-effectiveness of drugs – has deemed the benefits of Orkambi to be too low for its high cost. Treatment costs £104,000 a year.

But new results from a phase III clinical trial suggest that the drug can stop the otherwise inexorable damage to the lungs that people with cystic fibrosis experience throughout their lives. The results also show that the drug can be beneficial for young children. At present, Orkambi is only approved in the EU for people over the age of 12.

“We’ve shown that even in younger patients who have relatively mild disease, Orkambi led to improvements in lung function,” says Felix Ratjen, of the Hospital for Sick Children at the University of Toronto, in Canada.

Oxygen boost

Ratjen’s team conducted a trial involving 204 children between the ages of 6 and 11. Of these, 103 received Orkambi twice a day for six months, while 101 received a placebo. At the end of the trial, those that took the drug showed improvements in two important measures of lung health.

Firstly, these children were 10 per cent better at taking in oxygen from their lungs. Secondly, the amount of chloride in their sweat dropped by around 20 per cent. Typically, people with cystic fibrosis have three times as much chloride in their sweat than other people – a result of having malfunctioning CFTR proteins.

“I think the results are important because they provide evidence that correcting the basic defect associated with the most common mutation of cystic fibrosis is also feasible in children,” says Carla Colombo of the University of Milan in Italy.

Ratjen says that longer-term trials are needed to prove Orkambi can halt cystic fibrosis damage, but the early signs are good. “The idea of early intervention is just that,” he says. “Intervene when the damage is still limited.”

Medhurst says the latest results will strengthen calls from the Cystic Fibrosis Trust and others for Orkambi to be made more widely available. “The case is significantly strengthened by these and other data emerging worldwide.”

As for people with cystic fibrosis who are genetically unable to benefit for Orkambi, a third drug called tezacaftor is being developed that might extend treatment to 90 per cent of all people with the condition. Early results suggest this drug and Kalydeco together can improve lung function in certain genetic types, and larger trials are planned.

Journal reference: Lancet Respiratory Medicine, DOI: 10.1016/S2213-2600(17)30215-1