Acebilustat is a small molecule inhibitor of Leukotriene A4 Hydrolase (LTA4H), the crucial enzyme in the production of the potent inflammatory mediator Leukotriene B4 (LTB4).
The anti-inflammatory drug has reduced the frequency of pulmonary exacerbations (PEx) and increased the time to next exacerbation over 48 weeks of therapy in the 200-patient, double-blind and placebo controlled study.
Acebilustat-treated patients showed 19% reduction in PEx and 22% reduced risk in progressing to first PEx against placebo, on a per protocol assessment.
The once-daily oral drug candidate is advancing to phase 3 development. It was designed to modulate the neutrophil driven immune response and bring the inflammation to homeostasis, enabling to avoid overactive inflammation.
According to the company, acebilustat has not showed any evidence of immunosuppression in preclinical studies or in clinical trials in humans, including healthy volunteers and CF patients.
Patients with less severe impairment of lung function achieved 34% reduction in PEx rate and 43% reduction in risk of experiencing their first exacerbation, as well as 96% increased likelihood of being exacerbation free after 48 weeks of treatment.
In addition, the patients concomitantly treated with CFTR modulator therapy showed a clinically meaningful 20% reduction in PEx, 29% increased time to first exacerbation and 47% higher likelihood of no exacerbations compared to patients treated with CFTR modulators and placebo.
Celtaxsys chief medical officer Sanjeev Ahuja said: “Acebilustat is notably the first novel anti-inflammatory molecule to prospectively demonstrate benefits in both reducing the frequency of pulmonary exacerbations and prolonging time to first exacerbation, when added to a CF patient’s existing treatment regimen in a clinical trial.
“We would like to thank all the patients who participated in this trial and their families who supported them. We are grateful to the study investigators and coordinators and our advisors who helped us design and execute the program.”
Celtaxsys is a privately-held drug discovery and development company engaged in the development of advanced treatments for serious inflammatory diseases.