idw – Informationsdienst Wissenschaft
Nachrichten, Termine, Experten
Nachrichten, Termine, Experten
MHH pneumologist investigates the effect of brensocatib on bronchiectasis disease in ASPEN study
Bronchiectasis are bulges in the bronchial tubes in the lungs. Viscous bronchial mucus collects in them, which is often difficult to cough up. This build-up of secretions is associated with chronic inflammation of the airways and provides the perfect breeding ground for bacteria and other pathogens, which in turn intensify the inflammation. The result is chronic, progressive lung disease. Most people affected suffer from constant coughing and sputum production, shortness of breath, fatigue, weight loss and frequent infections that require antibiotic therapy. The protrusions are irreversible and the disease cannot yet be cured. There is currently no standardised treatment for bronchiectasis. Although national and international guidelines recommend physiotherapeutic respiratory therapy, mucolytic agents and antibiotics to treat the infections, the approaches do not adequately address the chronic inflammation and the threat of disease progression. If lung function is too severely impaired at some point during the course of the disease, the only remaining treatment option is a lung transplant.
The results of the ASPEN study, the largest global clinical study on bronchiectasis disease to date, in which more than 1700 patients took part, now offer hope. The anti-inflammatory effect of the investigational drug brensocatib was analysed. The ASPEN study showed that brensocatib in tablet form in doses of ten and 25 milligrams reduced the likelihood of exacerbations in relapses requiring antibiotic treatment by around 20 per cent. In addition, treatment with 25 milligrams of brensocatib significantly slowed the deterioration in lung function and thus also improved the quality of life of those affected. The results of the ASPEN study have been published in the renowned ‘New England Journal of Medicine’. Professor Dr Felix Ringshausen, Senior Physician at the Clinic for Pneumology and Infectiology at Hannover Medical School (MHH) and Head of the Bronchiectasis Outpatient Clinic, was the only scientist from Germany involved in the scientific publication of the study results. His conclusion: ‘Brensocatib is the first active substance that treats the cause of the disease and will probably be the first drug to be approved for the treatment of bronchiectasis disease. ’The drug is due to be launched on the US market this summer. Marketing authorisation in Europe is expected to be granted at the end of this year or early next year.
Excessive bacterial defence
Bronchiectasis can be caused by congenital lung diseases such as cystic fibrosis or primary ciliary dyskinesia (PCD). However, they develop much more frequently after severe infectious diseases such as pneumonia or tuberculosis, uncontrolled asthma or due to chronic obstructive pulmonary disease (COPD).
In most cases, inflammatory processes damage the walls of the bronchial tubes and destroy the elastic connective tissue of the lungs. As a result, the self-cleaning of the lungs, known as mucociliary clearance, is disrupted.
This cycle of inflammation, impaired mucociliary clearance, structural damage to the airways and recurring infections is further intensified by so-called neutrophil granulocytes. They belong to the white blood cells and fight infections with bacteria as part of the immune system. Their weapons include enzymes called serine proteases. When the granulocytes mature in the bone marrow, these serine proteases are switched on, so to speak. This task is performed by the protein dipeptidyl peptidase 1 (DDP-1). ‘In chronic airway inflammation such as bronchiectasis disease, however, the very effective bacterial police of the neutrophil granulocytes overshoots the mark and releases too many serine proteases into the airway,’ explains Professor Ringshausen. These then not only damage the pathogens in the airways, but also the bronchial walls and the surrounding lung tissue. As a result, the body's own lung cleansing system functions even more poorly, creating an incessant vicious circle of inflammation, damage to the airways and recurring infections, which promotes the progression of bronchiectasis disease.
Few side effects
Brensocatib interrupts this vicious circle by blocking the protein DDP-1 and mitigating the activation of serine proteases. The advantage: the active substance is a reversible inhibitor, meaning that it does not irreversibly switch off production. ‘If brensocatib is discontinued, it no longer blocks DDP-1, which can then reactivate the enzymes to their full extent and strengthen the bacterial defence,’ says Professor Ringshausen. In the ASPEN study, the patients treated with the active substance in addition to their usual therapy remained symptom-free for longer than the control group, who only received a placebo, i.e. a dummy preparation without active substance. The side effects were also limited. Despite the reduced effectiveness of the neutrophil granulocytes, the patients treated with bensocatib did not suffer from bacterial infections more frequently than the control group. Only the cases of dry skin increased slightly.
A positive result, emphasises the bronchiectasis expert: ‘Brensocatib reduced the risk of worsening symptoms, slowed the deterioration of lung function and thus convincingly improved the quality of life of those affected.’
For further information, please contact Professor Dr Felix Ringshausen, ringshausen.felix@mh-hannover.de, telephone (0511) 532-3595.
The original paper ‘Phase 3 Trial of the DPP1 Inhibitor Brensocatib in Bronchiectasis’ can be found here: https://www.nejm.org/doi/full/10.1056/NEJMoa2411664
As part of the international ASPEN study, Professor Dr Felix Ringhausen investigated how the active ...
Karin Kaiser/MHH
Criteria of this press release:
Journalists
Medicine
transregional, national
Research results, Transfer of Science or Research
English
As part of the international ASPEN study, Professor Dr Felix Ringhausen investigated how the active ...
Karin Kaiser/MHH
You can combine search terms with and, or and/or not, e.g. Philo not logy.
You can use brackets to separate combinations from each other, e.g. (Philo not logy) or (Psycho and logy).
Coherent groups of words will be located as complete phrases if you put them into quotation marks, e.g. “Federal Republic of Germany”.
You can also use the advanced search without entering search terms. It will then follow the criteria you have selected (e.g. country or subject area).
If you have not selected any criteria in a given category, the entire category will be searched (e.g. all subject areas or all countries).
