Celtaxsys gains US clearance for Phase 2 trial of acebilustat in patients with cystic fibrosis

Celtaxsys has gained clearance from the US Food and Drug Administration (FDA) to begin a Phase 2 clinical trial of acebilustat in adult patients with cystic fibrosis (CF) in the US.

The regulatory submissions to the health authorities in Europe will be filed soon after. This groundbreaking clinical study, testing the lung function preservation effects of once-daily oral acebilustat treatment over 48 weeks, was designed in consultation with Cystic Fibrosis Foundation Therapeutics (CFFT).

CF is a life-threatening disease that affects the lung and digestive system and impacts about 70,000 patients worldwide. CF is caused by mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene leading to abnormal CFTR protein functioning, the result of which causes the body to accumulate excessive levels of unusually thick mucus in the lungs. This excessive sticky mucus in the lungs is a site for infections that can require hospitalization. Respiratory distress in CF, defined as acute difficulty in breathing, infection and/or hospitalization, is most commonly related to lung infection and inflammation induced lung tissue damage attributable to an overwhelming and dysfunctional response by dysregulated neutrophils. Treatment of this lung inflammation is, therefore, thought to be key to improving CF patients’ lung health and well-being.

Acebilustat treatment may potentially address lung inflammation in patients with CF

“We believe this day marks another watershed moment in the development of new therapeutics for CF patients. While the advent of important new therapies, including CFTR modulators, has been a true game-changer for many CF patients, lung inflammation continues to be a primary cause of CF patient morbidity and mortality,” said Greg Duncan, Celtaxsys CEO. “Once-daily oral acebilustat treatment can potentially address the underlying inflammation that results in irreversible lung function decline and occurs in all CF patients, independent of CFTR genotype.”

Added Sanjeev Ahuja, MD and Chief Medical Officer at Celtaxsys, commented, “The interplay between infection and inflammation is the main driver for lung function decline in CF. Finding a proper balance in immune modulation is key to treating the inflammation and resultant decline in lung function without increasing risk of infection. In a previous clinical trial in CF patients, acebilustat reduced important biomarkers of lung and systemic inflammation without apparent increased susceptibility to infection. Anti-inflammatory agents, such as acebilustat, could work by slowing the progression of disease over time, but do require a longer duration of assessment to best judge their long term benefits.  Importantly, acebilustat should be complementary to existing CF therapies, including the new CFTR modulators, and may actually help boost their efficacy by reducing the pool of neutrophil elastase enzyme in the lungs that can degrade functional CFTR in these patients.”

This Phase 2 CF trial is slated to begin in the US by October this year.