An Exhaustive Monograph on Casopitant (DB06634): A Highly Efficacious Neurokinin-1 Antagonist Derailed by Pharmacokinetic Liabilities

Executive Summary

Casopitant (DrugBank ID: DB06634) is an investigational small molecule drug developed by GlaxoSmithKline as a potent, selective, and centrally-acting neurokinin-1 (NK1) receptor antagonist.[1] Its primary therapeutic target was the prevention of chemotherapy-induced nausea and vomiting (CINV), a significant and debilitating side effect of cancer treatment. The development program for Casopitant progressed through extensive Phase III clinical trials, where it demonstrated robust and statistically significant efficacy. When added to the standard-of-care antiemetic regimen (a 5-HT3 receptor antagonist and a corticosteroid), both oral and intravenous formulations of Casopitant consistently improved the control of emesis in patients receiving both highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC).[3] The drug proved superior to control regimens, achieving a complete response (defined as no emesis and no use of rescue medication) in a significantly higher proportion of patients over the critical 5-day post-chemotherapy period.[3]