Acebilustat (formerly CTX-4430) is an oral anti-inflammatory designed to reduce the production of leukotriene B4 (LTB4), a molecule that causes inflammation and is known to be elevated in people with cystic fibrosis (CF). Reducing inflammation helps to prevent tissue damage in the lungs for patients with CF.1
How acebilustat works
Lung inflammation caused by high levels of white blood cells is a major source of complications for people with CF. In order to address lung inflammation, acebilustat targets the excessive amount of white blood cells in the lungs of cystic fibrosis patients.
The therapy, being developed by Celtaxsys, is based on a small molecule that inhibits leukotriene A4 hydrolase (LTA4H), which is the principal enzyme in the production of leukotriene B4 (LTB4). Researchers have found that LTA4H and LTB4 are strongly associated with the development of many conditions that involve inflammation, including CF.2
Studies involving acebilustat
A Phase 1 study of acebilustat (NCT01944735) showed that just two weeks of treatment reduced lung inflammation in people with CF. The study was a randomized, double-blind, placebo-controlled, and dose-escalation Phase 1 trial, in which the effects of two doses of acebilustat (50 mg and 100 mg orally, once daily for 15 days) were evaluated using lung and systemic biomarkers. According to published data, treatment with acebilustat at 100 mg reduced white blood cell counts (sputum neutrophil counts) and tissue damage in the lungs of people with CF by 65%. The researchers also showed that both groups of treated participants had a 58% reduction in sputum neutrophil elastase (a biomarker that predicts the decline of lung function) compared to the placebo group. Participants also had a lower C-reactive protein and sputum neutrophil DNA, which are other biomarkers related to lung inflammation. In general, acebilustat was safe and well-tolerated at both doses.
A Phase 2 study EMPIRE-CF (NCT02443688) is currently recruiting participants in North America and Europe, and will evaluate the safety and efficacy of acebilustat (50 mg and 100 mg) administered once daily for 48 weeks. People with CF with any type of mutations in the CFTR gene can participate, and acebilustat can be administered in this study with other therapies, including Kalydeco and Orkambi.
Acebilustat has received Orphan Drug designation for the treatment of CF in the US and Europe.
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