![](https://thelimbic.com/wordpress/wp-content/uploads/2018/10/Ian-Balfour-Lynn-300x273.jpg)
Dr Ian Balfour-Lynn
There are both promising therapies and emerging problems in the future management of cystic fibrosis, according to a UK paediatric respiratory physician.
Dr Ian Balfour-Lynn, director of paediatric CF at the Royal Brompton Hospital, told ERS 2018 that phase 2 studies of CFTR modulating therapies showed they had a ‘genuine disease modifying effect’.
As a result a number of phase 3 trials using combinations of drugs were underway and trials extending the age groups for treatment were maturing.
He said groundbreaking recent studies included the use of ivacaftor (Kalydeco) in 1-2 year olds. The ARRIVAL study showed safety although significantly raised liver function tests in some patients suggested clinicians would need to be vigilant.
While the study was small, biomarkers suggested ivacaftor worked even better in the younger children than in 2-5 years olds, with sweat chloride reducing by an impressive mean of 74 mmol/L.
“And as with all the ivacaftor studies, this happens within the first fortnight.”
Dr Balfour-Lynn said mean stool elastase increased by 165 ug/g suggesting that starting as soon as possible as may help restore pancreatic function.
Recently published US and UK registry data also supported the disease modifying nature of the CFTR potentiator, with reductions in mortality, transplantation, hospitalisation and exacerbations.
“That’s very important to persuade regulatory bodies that they need to keep paying for these drugs and that the longer term outcomes really are likely to change,” he said.
A recent study of the lumacaftor and ivacaftor combination (Orkambi) in patients from 12 years of age and homozygous for F508del demonstrated its effect on CTFR function with improvements in sweat chloride, nasal potential difference and intestinal current measurement.
The combination has been licensed for 6-11 years olds in Europe and 2-5 years olds in the US.
Similarly, the tezacaftor and ivacaftor (Symdeko/Symkevi) combination in over 12 year olds homozygous for Phe508del improved FEV1, exacerbations and sweat chloride. It appeared to have similar efficacy but improved safety than its competitor, he said.
The FDA approved the combination earlier in the year and the European Medicines Agency had also given it a positive opinion in July.
Dr Balfour-Lynn said the triple combination drugs coming through for CF were probably much more exciting – assuming the phase 3 studies underway confirmed findings from the phase 2 studies.