In a significant advance in cystic fibrosis treatment, researchers at Imperial College London are leading a groundbreaking human trial of an innovative inhalation gene therapy that could benefit the trial regardless of its gene mutation type. The treatment, known as BI 3720931, represents the potential lifeline of 10-15% of patients who cannot benefit from current therapies.
The Lenticlair 1 trial covers multiple European countries and aims to use lentiviral vectors to perform new approaches – modified viruses that can deliver functional genes to patient cells. This approach could mark a turning point in treating disease in about 105,000 people around the world.
“The UK CF Gene Therapy Alliance is very excited to reach this milestone after 24 years of focused efforts,” said Professor Eric Alton, who was trialed at the Imperial National Heart & Lung Institute. “While the direct target is those who do not meet CFTR modulators, this novel therapy has the potential to provide long-lasting improvement in CF function and disease modification in patients with CF without regard to their mutation type.”
Cystic fibrosis is a genetic disease that gradually worsens over time, and due to CFTR gene defects, thick, sticky mucus is produced in the lungs and digestive system. Due to more than 2,000 known mutations in this gene, the severity of the disease varies greatly among patients. Current treatments work for many people, but leave a critical gap for those with certain genetic characteristics.
The new therapy provides a more comprehensive solution by inserting functional copies of the CFTR gene into the DNA of airway epithelial cells. Professor Jane Davies, the principal investigator of the UK trial, highlighted the progress of existing treatments and the urgent need for alternatives.
“It’s incredible that people who witness the health benefits of CFTR modulators, but who cannot benefit from these drugs, urgently need alternative treatments,” Davis noted. “We broke through gene therapy in this trial New foundations are provided by the gene therapy with long-lasting CFTR expression.”
The trial, conducted in collaboration with biopharmaceutical companies Boehringer Ingelheim and Oxb (formerly Oxford Bioorganization), will involve approximately 36 participants in the UK, France, Italy, the Netherlands and Spain. The study was divided into two phases: initial safety and dose discovery phase, followed by a randomized, double-blind placebo-controlled study to evaluate clinical efficacy.
The reason for setting this treatment is that flexibility can be achieved in a long-term treatment plan if needed. After the initial 24-week trial period, participants will continue a long-term follow-up study called Lenticlair-on, which is expected to end in early 2027.
The technology behind the treatment is lentiviral vectors, representing complex applications of genetic engineering. These modified viruses naturally insert genetic material into host cells, making them an ideal vehicle for gene therapy. The team used this ability to correct the potential genetic causes of cystic fibrosis.
Davies acknowledges the key role of patients participating in medical research: “I want to admit that with people with CF prepare time for trials of new drugs, we would not be able to do this without us.”
For those interested in following the trial progress, additional information can be obtained through ClinicalTrials.gov with nct06515002 identifier.
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