Inhalable gene therapy tested for cystic fibrosis treatment in the UK and Europe

An inhalable medicine with the potential to improve lung disease in people with cystic fibrosis, irrespective of their mutation type, is being tested in human trials in the UK and Europe.

Cystic fibrosis (CF) is caused by defects in the CFTR gene, which causes a buildup of thick sticky mucus in the lungs and digestive system. It causes lung infections and gradually affects the ability to breathe. The new lentiviral vector-based gene therapy works by inserting a functioning copy of the CFTR gene in the DNA of the epithelial cells in a patient's airway. 

At present, some people with CF respond well to relatively new treatments known as CFTR modulator medicines, which work by targeting the related CFTR protein. However, these are not an option for around 10-15% of patients. 

The aim of the new treatment being trialled, known as BI 3720931, is to improve lung function and reduce exacerbations (flare-ups, often leading to hospitalisation), for people with CF irrespective of their mutation type – including those who genetically cannot benefit from other CF therapies.

The LENTICLAIR 1 trial, which will evaluate the safety, tolerability, and efficacy of the treatment, is being conducted by biopharmaceutical company Boehringer Ingelheim in partnership with the UK Respiratory Gene Therapy Consortium (GTC) and OXB (formerly Oxford Biomedica). Around 36 men and women with cystic fibrosis will be treated at centres in the UK, France, Italy, Netherlands and Spain.

Cystic fibrosis is an inherited lifelong disease that gets worse over time. It is estimated to affect 105,000 people worldwide. There are more than 2,000 known mutations in the CFTR gene, which lead to different levels of the severity of the disease.

Lentiviral vectors are a type of gene therapy that exploit the ability of lentiviruses to infect human cells. Lentiviruses are a family of viruses that infect by inserting their genetic material into their host cell's genome. By modifying lentiviruses, scientists have been able to use them as a vehicle to insert beneficial genes into cells. 

Professor Eric Alton, Professor of Gene Therapy and Respiratory Medicine at Imperial's National Heart & Lung Institute, is leading the trial. He coordinates the UK CF Gene Therapy Consortium, which brings together the three centres in the UK (Edinburgh and Oxford Universities and Imperial College London) who are focused on translational respiratory gene therapy. He is also an Honorary Consultant Physician at the Royal Brompton Hospital, one of the UK trial centres.

The UK CF Gene Therapy Consortium is very excited to have reached this milestone after 24 years of focused effort and in close collaboration with our funding partners. While the immediate target are those patients who are not eligible for CFTR modulators, this novel therapy has the potential to achieve long-lasting CFTR function improvement and disease modification for people with CF irrespective of their mutation type and importantly has the potential for re-dosing if needed."

Professor Eric Alton, Professor of Gene Therapy and Respiratory Medicine at Imperial's National Heart & Lung Institute

Professor Jane Davies of Imperial's National Heart and Lung Institute, who is UK Lead Investigator for the trial, said: "It's been incredible to witness the health benefits afforded by CFTR modulators, but those who cannot benefit from these drugs urgently need alternative treatments. We're breaking new ground in this trial with a gene therapy which has the potential for long-lasting CFTR expression. I'd like to acknowledge the people living with CF who are prepared to give their time to trials of new drugs, without whom we'd be unable to make this sort of progress."

In the first phase of the trial, different doses of the treatment will be given to evaluate safety, tolerability and select doses for Phase II. In the second phase, two selected doses or placebo will be given in a randomised, double-blind placebo-controlled dose expansion study to assess clinical efficacy and safety.

After completion of the 24-week trial period, trial participants will take part in a long-term follow-up study, LENTICLAIR-ON.

The trial is expected to be completed in early 2027. Additional information about the trial is available via ClinicalTrials.gov at NCT06515002.