Cystic Fibrosis Gene Therapy Clinical Trial Demonstrates Beneficial Effect on Lung Function

Friday, July 3rd 2015

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Repeated nebulisation of non-viral CFTR gene therapy in patients with cystic fibrosis: a randomised, double-blind, placebo-controlled, phase 2b trial.

Lancet Respiratory Medicine, 2015, In Press.

The current trial was launched in 2012 and funded by a partnership between the Medical Research Council & the National Institute for Health Research


Results Overview

A therapy that replaces the faulty gene responsible for cystic fibrosis in patients' lungs has produced encouraging results in a major UK trial conducted by the UK Cystic Fibrosis Gene Therapy Consortium (UKCFGTC).

One hundred and thirty six patients aged 12 and above were randomly assigned to either 5ml of nebulised pGM169/GL67A (gene therapy) or saline (placebo) at monthly intervals over 1 year. Lung function was evaluated using a common clinical measure FEV1.

The clinical trial reached its primary endpoint with patients who received therapy having a significant, if modest benefit in lung function compared with those receiving a placebo. After a year of treatment, in the 62 patients who received the gene therapy, FEV1 was 3.7% greater compared to placebo. This was a result of stabilisation of respiratory function rather than an improvement.


Timecourse of the FEV1 response to either placebo or pGM169/GL67A View in new tab


However, the effects were inconsistent, with some patients responding better than others. In particular, in the half of patients with the worst lung function at the start of the study, there was a doubling of the treatment effect, with changes in FEV1 of 6.4%.


Time course of the FEV1 response stratified by baseline FEV1 at trial entry. Error bars indicate SEM.
A - Baseline FEV1 50-70% predicted. B - Baseline FEV1 70-90% predicted.
View in new tab


Patients from across England and Scotland participated, and were treated in two centres, Royal Brompton Hospital in London and the Western General Hospital in Edinburgh.

The trial is the first ever to show that repeated doses of a gene therapy can have a meaningful effect on the disease and change the lung function of patients. Nevertheless, the Consortium believe more research is needed to improve the effectiveness before the therapy will be suitable for clinical use.



The UKCFGTC is a group of scientists and clinical teams from Imperial College London, University of Oxford, University of Edinburgh, Royal Brompton & Harefield NHS Foundation Trust and NHS Lothian who came together in 2001 to develop a gene therapy, supported then by the Cystic Fibrosis Trust.

The current trial was launched in 2012 and funded by a partnership between the Medical Research Council (MRC) and the National Institute for Health Research (NIHR). The findings are published today in The Lancet Respiratory Medicine.


What is Cystic Fibrosis?

Cystic fibrosis (CF) is the commonest lethal inherited disease in the UK, affecting around 10,000 people nationally and over 90,000 worldwide. Patients' lungs become filled with thick sticky mucus and they are vulnerable to recurrent chest infections, which eventually destroy the lungs.

The cause of CF, mutations in a gene located on chromosome 7, was identified in 1989, opening the door to introducing a normal copy of this gene using gene therapy. In the trial, patients were treated by inhaling molecules of DNA wrapped in fat globules (liposomes) that deliver the gene into the cells in the lung lining.


Quotes about the Trial

“Patients who received the gene therapy showed a significant, if modest, benefit in tests of lung function compared with the placebo group and there were no safety concerns. Whilst the effect was inconsistent, with some patients responding better than others, the results are encouraging.”

Prof Eric Alton,  Senior Co-author, Consortium Coordinator, Imperial College London & consultant physician at Royal Brompton Hospital.


“Stabilisation of lung disease in itself is a worthwhile goal. We are actively pursuing further studies of non-viral gene therapy looking at different doses and combinations with other treatments, and more efficient vectors.”

Prof Stephen Hyde, Senior co-author, University of Oxford.


“Publication of this trial is a landmark for cystic fibrosis patients and we are particularly grateful to the many patients across the UK who gave their time and effort to participate and make this collaborative venture a success.” 

Dr Alastair Innes, Senior co-author, Western General Hospital, Edinburgh.


"We are committed to improving and transforming the lives of people with cystic fibrosis, and the results of this pioneering clinical trial are a promising development. Further clinical research is now needed before we can say that it is a viable clinical therapy but it is encouraging that a proof of concept has been established."

Ed Owen, Chief Executive, Cystic Fibrosis Trust.


 "Cystic Fibrosis can have a devastating effect on patients and families and this is an excellent development for people living with the condition. The government is absolutely committed to supporting new medical treatments and invests £1bn a year in health research. It is vital we are at the forefront of turning scientific discoveries into tangible benefits and affordable treatments for NHS patients."

George Freeman MP, Minister for Life Sciences.


Further Information

Imperial Innovations, Imperial's technology commercialisation company, is acting as the lead technology transfer office for the Consortium. Innovations holds a family of patents and orphan drug designation for the treatment, and is seeking commercial partners who can support its further clinical development.

The Consortium is developing a second therapy that uses a virus to deliver the DNA into cells. We are aiming to begin the first clinical trial of this treatment in 2016. "Our aim is to achieve a step change in the treatment of CF that focuses on the basic defect rather than just addressing the symptoms. It has taken more than 20 years to get where we are now, and there is still some way to go. Eventually we hope gene therapy will push CF patients towards a normal life expectancy and improve their quality of life significantly," said Professor Alton.


View from a Patient on the Trial

Mary and her mother at the press briefing event in London.The trial could not have happened without the incredible dedication of the patients and their families. It is only fitting therefore that we end this announcement with some words from one of them.

Mary Bondonno 16 from Surrey*, took part in the trial and was given the gene therapy. Mary’s lung function went from 66.72 per cent to 80.29 per cent at the end.

“Before the trial I found it very difficult to clear my lungs of mucus, I spent a lot of time in hospital because of repeated infections. Activities like PE at school would leave me out of breath very quickly."

"This all changed for me once I went on the trial and within a month of getting the first dose of the gene therapy I noticed improvements in my condition. I was able to clear my lungs better, concentrate more at school because I wasn’t as tired and I was able to do more with my family like go for walks with them for long periods of time."

"It felt good to see my condition improving and I felt better overall. I had a great experience on the trial and I’m glad that I took part in it because the gene therapy had such a positive impact on my life.” 

*We received Mary's permission to include her details here.

Press Releases (PDF)


The Lipid GL67A (red lid) and plasmid pGM169 (blue lid)



The formulation was delivered to patients' lungs via a nebuliser View in new tab


Sheep lung parenchyma (cell nuclei blue) transduced with an adenoviral vector (green).


Purifying mRNA from tissue samples.


Schematic diagram of the large human airways.


Proposed 3D model of the CFTR protein.


A CFTR Western blot, to confirm protein production in cell culture.


Mouse lung large airway (cell nuclei blue) transduced with an adenoviral vector (green).


A frozen vial of GL67A (left) and a frozen vial of pGM169 plasmid DNA (right)


A pellet of E.coli containing a plasmid expressing a pink fluorescent protein.


DNA fragments being cut from an agarose gel exposed to UV.


Pellets of DNA following precipitation.


E.coli from a large scale industrial production of our clinical trial plasmid pGM169.


Human airway liquid interface cultures transduced with a lentivirus expressing Luciferase.


Large scale lentivirus production in suspension culture.


Light microscope image of a human airway liquid interface cultures. Dark patches are mucous.