Once-daily acebilustat, an investigational oral therapy for cystic fibrosis (CF) under development by Celtaxsys, reduces the frequency and delays the onset of pulmonary exacerbations in CF patients, results from a Phase 2 study show.
Patients with better lung function benefited most, with a 96% higher chance of being free of exacerbations after 48 weeks of treatment, compared with a placebo.
Pulmonary exacerbations (the acute worsening of lung symptoms) are common throughout the life of a CF patient. Episodes generally include an increase in respiratory symptoms (e.g., increased cough, sputum production, shortness of breath) along with an acute decline in lung function.
Acebilustat reduces the excessive number of white blood cells in the lungs by inhibiting the production of leukotriene B4 (LTB4), a potent inflammatory mediator. This molecule is involved in the activation and attraction of white blood cells to inflammation sites, and has been strongly implicated in many inflammatory conditions, including CF.
Celtaxsys has completed a Phase 2 study, called EMPIRE-CF (NCT02443688), evaluating the efficacy and safety of acebilustat. In the study, 200 CF patients recruited in clinical centers across the United States, Canada, and Europe were randomly assigned to receive either acebilustat 50 mg, 100 mg, or a placebo, once daily for 48 weeks.
Compared with a placebo, acebilustat was seen to reduce by 19% the frequency of pulmonary exacerbations, and led to a 22% reduction in patients’ chances of having their first exacerbation.
This clinical benefit was more meaningful in patients being treated simultaneously with acebilustat and CFTR modulator medications (CFTR is the gene defective in CF patients). Treatment led to a 20% reduction in pulmonary exacerbations, a 29% longer time to first exacerbation, and a 47% higher likelihood of no exacerbations, compared to patients treated with CFTR modulators and placebo.
Acebilustat treatment was seen to most favor with less severe impairment of lung function (a percent predicted forced expiratory volume in 1 second higher than 75%). Among these patients, the drug led to a 35% reduction in the rate of pulmonary exacerbations, a 43% reduction in the risk of experiencing an exacerbation for the first time, and increased by 96% the odds of having no exacerbations after 48 weeks of treatment.
Acebilustat was well-tolerated and did not increase the risk of infection. In acebilustat-treated patients, the most common adverse events were infective pulmonary exacerbation, cough, coughing up blood, a common cold, headache, and increased sputum. These were all mild or moderate in severity.
“These data showed that acebilustat has the potential to reduce the rate of pulmonary exacerbations in CF patients, including patients on a CFTR modulator. This is a critically important health outcome for the CF population that we expect to explore further,” Greg Duncan, chief executive officer of Celtaxsys, said in a press release.
Celtaxsys is receiving support from the Cystic Fibrosis Foundation to advance acebilustat into Phase 3 clinical testing, and to confirm the efficacy and safety of the drug in CF patients.