Phase 1/2 trial of inhaled gene therapy for CF recruiting in Europe
BI 3720931 to be tested in people not eligible for modulator therapy
Boehringer Ingelheim has launched a Phase 1/2 clinical trial of BI 3720931, an inhaled gene therapy designed to treat cystic fibrosis (CF).
The first-in-human trial, dubbed LENTICLAIR 1 (NCT06515002), is expected to enroll about 36 adults with CF who are not eligible for treatment with CFTR modulators. In the study’s Phase 1 part, participants will be given BI 3720931 at one of three ascending doses with a main goal of assessing safety. In its subsequent Phase 2 portion, patients either be given one of two therapy doses or a placebo, with a main goal of seeing how the treatment affects markers of lung function after about two months.
Eligible adults are being recruited at sites in Italy, France, and the U.K. Additional sites in these countries, as well as in the Netherlands and Spain, are expected soon to begin enrolling patients.
“We are very excited about the start of the LENTICLAIR 1 First-In-Human trial and how BI 3720931 could potentially improve the lives of people living with CF, and who are unable to benefit from current CFTR modulators,” Paola Casarosa, PhD, a member of the board of managing directors at Boehringer with responsibility for its innovation unit, said in a company press release.
Therapy aiming to deliver a healthy gene copy to cells in patients’ lungs
CF is caused by mutations in the gene CFTR, which provides instructions to make a protein with the same name. Lack of functional CFTR protein causes the body to produce unusually thick and sticky mucus, which builds up and causes problems with organs, particularly the lungs and digestive system.
CFTR modulators are a recent class of medicines that can boost the activity of the mutated protein, but they only work in people who carry specific CFTR mutations. Around 1 in 10 CF patients are not eligible for modulator treatment.
BI 3720931 is an inhaled gene therapy that aims to deliver a healthy copy of the CFTR gene to cells in the lungs. As such, the therapy is designed to allow lung cells to make a functional CFTR protein, ultimately normalizing mucus production and easing lung-related CF symptoms. Since it delivers a healthy gene, the therapy is expected to work in patients regardless of what specific mutations they carry.
Boehringer, which acquired therapy rights in 2021 and has been collaborating in its development since 2018, is focused on patients who aren’t eligible for CFTR modulators, aiming to provide more treatment options to people who currently lack them.
The LENTICLAIR 1 clinical trial is being conducted in partnership with the U.K. Respiratory Gene Therapy Consortium (GTC), a coalition of scientists in the U.K. focused on bringing gene therapy to people with CF.
“The GTC is very excited to have reached this milestone after 24 years of focused effort and in close collaboration with our partners and people with CF,” said Eric Alton, a professor at Imperial College London who coordinates the consortium. “While the immediate target are those adult 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 mutation type and has the potential for re-dosing if needed.”
Also helping with the trial is OXB, a company that specializes in making viral vectors — viruses that have been modified to deliver a therapeutic gene instead of causing an infection. BI 3720931 uses such a lentiviral vector to deliver the CFTR gene.
Casarosa said that the partnership between Boehringer, GTR, and OXB “provides an excellent example of the progress that can be made when diverse organizations and people come together with a long-term, shared goal to create a new paradigm of care.”
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