In a significant advancement for cystic fibrosis treatment, researchers at Imperial College London are leading groundbreaking human trials of an innovative inhaled gene therapy that could benefit patients regardless of their genetic mutation type. The treatment, known as BI 3720931, represents a potential lifeline for the 10-15% of patients who cannot benefit from current therapies.
The LENTICLAIR 1 trial, spanning multiple European countries, aims to evaluate a novel approach using lentiviral vectors – modified viruses that can deliver functional genes to patients’ cells. This method could mark a turning point in treating a disease that affects approximately 105,000 people worldwide.
“The UK CF Gene Therapy Consortium is very excited to have reached this milestone after 24 years of focused effort,” said Professor Eric Alton, who leads the trial at Imperial’s National Heart & Lung Institute. “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.”
Cystic fibrosis, an inherited condition that progressively worsens over time, creates a buildup of thick, sticky mucus in the lungs and digestive system due to defects in the CFTR gene. With over 2,000 known mutations of this gene, the severity of the disease varies significantly among patients. Current treatments, while effective for many, leave a crucial gap in care for those with certain genetic profiles.
The new therapy works by inserting a functioning copy of the CFTR gene into the DNA of airway epithelial cells, potentially offering a more comprehensive solution. Professor Jane Davies, UK Lead Investigator for the trial, emphasized both the progress made with existing treatments and the urgent need for alternatives.
“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,” Davies noted. “We’re breaking new ground in this trial with a gene therapy which has the potential for long-lasting CFTR expression.”
The trial, conducted in partnership with biopharmaceutical company Boehringer Ingelheim and OXB (formerly Oxford Biomedica), will involve approximately 36 participants across centers in the UK, France, Italy, Netherlands, and Spain. The study is structured in two phases: an initial safety and dose-finding phase, followed by a randomized, double-blind placebo-controlled study to assess clinical efficacy.
What sets this treatment apart is its potential for re-dosing if needed, offering flexibility in long-term treatment plans. After the initial 24-week trial period, participants will continue in a long-term follow-up study called LENTICLAIR-ON, with the entire trial expected to conclude in early 2027.
The technology behind the treatment, lentiviral vectors, represents a sophisticated application of genetic engineering. These modified viruses naturally insert genetic material into host cells, making them ideal vehicles for gene therapy. The research team has harnessed this capability to potentially correct the underlying genetic cause of cystic fibrosis.
Davies acknowledged the crucial role of patient participation in advancing medical research: “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.”
For those interested in following the trial’s progress, additional information is available through ClinicalTrials.gov under the identifier NCT06515002.