Acebilustat inhibits an enzyme that takes part in the production of a substance called leukotriene B4 (LTB4) that promotes an immune response known as inflammation. Scientists believe LTB4 plays a key role in the development of diseases like CF that stem from inflammation.
A hallmark of CF is a buildup of mucus in the lungs that is a perfect environment for bacteria to grow. The buildup can lead to an excessive inflammatory response characterized by a surge in immune cells in the lungs, compromising a patient’s ability to breathe.
Acebilustat reduces the surge, decreasing inflammation and improving breathing.
A Phase 1 trial showed that two weeks of acebilustat reduced the number of immune cells called neutrophils in patients’ lungs. It also decreased levels of a marker of inflammation called C-reacive protein.
“We believe the anti-inflammatory activity of acebilustat has the potential to preserve lung function and reduce pulmonary exacerbations in CF patients” when combined with standard therapies, Greg Duncan, Celtaxsys’ president and chief executive officer, said in a press release. This is true regardless of the mutation of the CFTR gene that causes a person’s cystic fibrosis, he said.
Celtaxsys is conducting a Phase 2 trial of acebilustat’s safety and ability to preserve CF patients’ lung function. The Cystic Fibrosis Foundation supported the idea of the trial and its design. Celtaxsys expects results by mid-2018.
“Although new therapies that correct CFTR [mutations] have markedly improved the outlook for patients with CF over the past few years, the effects of chronic inflammation in the lungs are still an important factor” in the disease’s progression and patients’ deaths, said Stuart Elborn, director of the Adult CF Center at Royal Brompton Hospital and Imperial College, London.
“An effective anti-inflammatory therapy for CF patients is a significant unmet medical need,” he said. “Acebilustat is an advanced-stage [therapy] development candidate in the CF anti-inflammatory pipeline” that has the potential to be an important treatment for the disease.
Both the U.S. Food and Drug Administration and the European Medicines Agency have designated acebilustat an orphan drug, a status that covers therapies for rare diseases. The designation offers companies incentives to develop a therapy and opens the way to its accelerated regulatory approval.