Fevipiprant is an oral, non-steroidal, highly selective, reversible antagonist of the
prostaglandin D2 (DP2) receptor. The DP2 receptor is a mediator of
inflammation expressed on the membrane of key inflammatory cells, including eosinophils, Th2 cells, type 2 innate lymphoid cells, CD8+ cytotoxic T cells, basophils and monocytes, as well as airway smooth muscle and epithelial cells. The DP2 receptor pathway regulates the allergic and non-allergic
asthma inflammatory cascade and is activated by the binding of
prostaglandin D2.
Fevipiprant is metabolised by several
uridine 5'-diphospho
glucuronosyltransferase enzymes to an inactive acyl-
glucuronide (AG) metabolite, the only major human metabolite. Both
fevipiprant and its AG metabolite are eliminated by urinary excretion;
fevipiprant is also possibly cleared by biliary excretion. These parallel elimination pathways suggested a low risk of major
drug-drug interactions (DDI), pharmacogenetic or ethnic variability for
fevipiprant, which was supported by DDI and clinical studies of
fevipiprant. Phase II clinical trials of
fevipiprant showed reduction in sputum
eosinophilia, as well as improvement in lung function, symptoms and quality of life in patients with
asthma. While
fevipiprant reached the most advanced state of development to date of an oral DP2 receptor antagonist in a worldwide Phase III clinical trial programme, the demonstrated efficacy did not support further clinical development in
asthma.