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LUSTER-1 and -2: Two randomized controlled trials of the prostaglandin D2 receptor 2 antagonist, fevipiprant, in asthma

Barbara Knorr

The prostaglandin D2 receptor 2 (DP2) pathway has an important mechanistic role in the pathophysiology of asthma; specifically, the potential benefits of blockage of this pathway as a treatment for asthma are of considerable interest. The DP2 receptor is expressed on cells involved in the inflammatory cascade, including T-helper type 2 (Th2) cells, eosinophils, type 2 innate lymphoid cells (ILC2), monocytes and basophils, as well as on airway epithelial and smooth muscle cells. Fevipiprant is an oral, highly selective DP2 receptor antagonist that has shown potent inhibitory effects on human eosinophils and Th2 cells in vitro. In Phase II clinical trials of patients with asthma, fevipiprant showed improvements in lung function, asthma control and quality of life. Furthermore, fevipiprant showed a reduction in sputum eosinophils, a biomarker for asthma exacerbations, as well as an effect on the airway epithelium and airway smooth muscle mass in patients with moderate-to-severe persistent asthma. In Phase II studies, fevipiprant showed a favorable safety profile. LUSTER-1 and -2 are replicate Phase III studies whose aim is to determine the efficacy, safety and tolerability of fevipiprant (150 mg and 450 mg once daily) added to standard-of-care asthma treatment in patients with symptomatic severe asthma over a one-year period.