Acebilustat (formerly CTX-4430) is an investigational oral drug under development by Celtaxsys. It’s currently being tested in a Phase 2 clinical trial as a modulator of inflammation in patients with cystic fibrosis (CF). The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have granted orphan drug status to acebilustat as a treatment for cystic fibrosis.

How acebilustat works

Inflammation develops when the immune system recognizes an external factor as a potential threat and triggers the migration and activity of immune cells to neutralize the offender. These cells spread a chemical “danger” signal to increase the inflammatory response and control the infection.

Acebilustat is a small molecule with the ability to decrease inflammation by reducing the production of a particular chemical messenger of the immune system called leukotriene B4 (LTB4), known to be involved in several inflammatory diseases. The drug works by inhibiting the enzyme that produces LTB4, thereby reducing the migration of immune cells to the sites of infection.

In CF patients, the accumulation of mucus in the lungs serves as a perfect environment for bacteria to grow. This triggers an excessive inflammatory response characterized by an overabundance of immune cells in the lungs, further compromising a patient’s breathing capacity.

Acebilustat is able to help CF patients by reducing the migration of immune cells to the lungs, therefore decreasing inflammation and improving breathing.

Studies with acebilustat

Celtaxsys has completed two Phase 1 clinical trials to assess the safety and tolerability of different oral doses of acebilustat when administered to healthy participants (NCT01748838) or to CF patients (NCT01944735).

Results showed that acebilustat was safe and well-tolerated in all participants. Two weeks of treatment reduced lung inflammation in people with CF and treatment with 100 mg of the drug reduced the immune cell count and tissue damage in the lungs of CF patients by 65 percent. The results also showed that treatment reduced the levels of several biomarkers related to lung inflammation.

The EMPIRE CF Phase 2b clinical trial (NCT02443688) is currently investigating the effectiveness of acebilustat in reducing lung inflammation and preserving lung function over the course of 48 weeks in CF patients who are at high risk for rapid lung function decline.

The multicenter placebo-controlled trial enrolled 200 CF patients in the U.S. and Europe and will compare two once-daily oral doses of acebilustat (50 mg and 100 mg). Acebilustat or a placebo are given concomitantly with standard CF care. Topline results are expected by mid-2018.

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