Case History: Discovery of Eribulin (HALAVEN™), a Halichondrin B Analogue That Prolongs Overall Survival in Patients with Metastatic Breast Cancer

Publisher Summary This chapter focuses on the discovery and development of eribulin. Eribulin mesylate (HALAVEN) is an antitubulin antimitotic agent with distinct microtubule end-binding properties that result in inhibition of microtubule dynamics in ways that differ from those of vinblastine and paclitaxel. This agent was recently approved by the U.S. Food and Drug Administration (FDA) for use in patients with metastatic breast cancer who have previously received at least two chemotherapeutic regimens for the treatment of metastatic disease. HALAVEN represents a new and exciting treatment option that for the first time has been shown to improve overall survival in heavily pretreated women with late stage breast cancer. The path leading to the discovery and development of eribulin included close three-way collaboration among the Kishi group at Harvard University, the National Cancer Institute (NCI), and Eisai. At many points along the drug discovery path, setbacks and roadblocks arose that threatened to derail the program. Nevertheless, each of the problems was solved in turn, thereby demonstrating that a structurally complex molecule could be optimized through total synthesis to successfully deliver a marketed drug that meets all pharmacological, toxicological, and physicochemical requirements.