A new inhalable gene therapy for cystic fibrosis (CF), BI 3720931, is being tested in a human trial across the U.K. and Europe. The trial, named LENTICLAIR 1, aims to determine the safety, tolerability, and efficacy of the treatment, particularly for patients who do not respond to CFTR modulator therapies. The study is sponsored by Boehringer Ingelheim in collaboration with the UK Respiratory Gene Therapy Consortium and OXB (formerly Oxford Biomedica).
CF is a genetic disorder caused by mutations in the CFTR gene, leading to thick mucus buildup in the lungs and digestive system. While CFTR modulator therapies have significantly improved outcomes for many patients, approximately 10–15% of individuals with CF do not benefit from these drugs. BI 3720931 uses lentiviral vector gene therapy to deliver a functional copy of the CFTR gene directly into airway cells, with the goal of improving lung function and reducing disease progression.
“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,” said Eric Alton, lead investigator of the trial and professor of gene therapy and respiratory medicine at Imperial College London. “This novel therapy has the potential to achieve long-lasting CFTR function improvement and disease modification for people with cystic fibrosis irrespective of their mutation type.”
How the trial works
The LENTICLAIR 1 study consists of two phases:
- Phase 1: Participants receive escalating doses of BI 3720931 to assess safety and determine appropriate dosing.
- Phase 2: Participants are randomly assigned to receive either one of two selected doses of BI 3720931 or a placebo in a double-blind, placebo-controlled study.
All participants will continue their standard CF treatments throughout the study. Researchers will monitor lung function and overall health through regular clinical assessments.
The trial will enroll around 36 adult participants at sites in the U.K., France, Italy, the Netherlands, and Spain. After completing the initial 24-week study period, participants will be followed in a long-term study, LENTICLAIR-ON, to assess the durability of the treatment’s effects.
Professor Jane Davies, U.K. lead investigator for the trial at Imperial’s National Heart and Lung Institute, emphasized the potential impact of the therapy: “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 that has the potential for long-lasting CFTR expression.”
Previous gene therapy efforts in CF
Gene therapy for cystic fibrosis has been an area of research for decades. Early trials using adenoviral and non-viral vectors faced challenges related to immune responses and limited duration of gene expression. The UK CF Gene Therapy Consortium previously conducted a Phase IIb trial in 2015 using a non-viral liposomal gene therapy, which showed modest improvements in lung function but required repeated dosing. Lentiviral vector-based therapies, like BI 3720931, are designed to enable longer-lasting gene expression and potentially reduce the need for frequent administration.
Looking ahead
The trial’s results will help determine whether BI 3720931 can offer a long-term treatment option for CF patients who currently lack effective therapies. While gene therapy holds promise, it remains experimental, and its clinical application will depend on the success of this and future trials.
If proven effective, lentiviral gene therapy could represent a significant step forward in treating CF and other genetic lung diseases. However, as with any investigational treatment, regulatory approval and larger studies will be required before it becomes widely available.
