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

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

An inhaled drug with the potential to improve lung disease in people with cystic fibrosis, regardless 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 thick, sticky mucus to build up in the lungs and digestive system. It causes lung infections and gradually affects the ability to breathe. The new lentiviral-based gene therapy works by inserting a working copy of the CFTR gene into the DNA of the epithelial cells in a patient's airway.

Currently, some people with CF respond well to relatively new treatments called CFTR modulator drugs, which target the associated CFTR protein. However, these are not an option for around 10-15% of patients.

The goal of the new treatment, known as BI 3720931, is to improve lung function and reduce exacerbations (flares that often lead to hospitalization) for people with CF, regardless of their mutation type - including those who are genetically unable to benefit from other CF therapies.

The Lenticlair 1 trial, which will assess the safety, tolerability and effectiveness of the treatment, is being conducted by Boehringer Ingelheim in collaboration with the UK's Breath Meat Therapy Consortium (GTC) and OXB (formerly Oxford Biomedica). Around 36 men and women with cystic fibrosis are being treated at centers in the UK, France, Italy, the Netherlands and Spain.

Cystic fibrosis is an inherited lifelong disease that worsens over time. It is estimated to affect 105,000 people worldwide. There are more than 2,000 known mutations in the CFTR gene, leading to varying degrees of disease severity.

Lentiviral vectors are a type of gene therapy that exploits the ability of lentiviruses to infect human cells. Lentiviruses are a family of viruses that infect by inserting their genetic material into the genome of their host cell. By modifying lentiviruses, scientists were able to use them as vehicles 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 centers in the UK (Universities and Universities and Imperial College London) focused on translational respiratory gene therapy. He is also an honorary consultant physician at the Royal Brompton Hospital, one of the UK trial centers.

The UK CF Gene Therapy Consortium is delighted to have reached this milestone after 24 years of focused effort and in close collaboration with our funding partners. While the immediate target is those patients who are ineligible for CFTR modulators, this novel therapy has the potential to provide long-lasting improvement in CFTR function and disease modification for people with CF regardless of their mutation type and, most importantly, has the potential to be re-dosed as needed. “

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

Professor Jane Davies, from Imperial's National Heart and Lung Institute, who is lead investigator in the UK, said: "It has been incredible to observe the health benefits of CFTR modulators, but those who cannot benefit from these drugs urgently need alternative treatments. New drugs without which we would not be able to make this kind of progress."

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

After completing the 24-week trial period, trial participants will participate in a long-term follow-up Lenticlair-on study.

The study is expected to be completed in early 2027. Additional information about the study can be found via ClinicalTrials.gov at NCT06515002.

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