Natural products have formed the basis of traditional medicine systems for thousands of years and have been the single most productive source of leads for the development of cancer drugs. This nomination describes the discovery of halichondrin B, a compound isolated from a species of marine sponge, and the subsequent preclinical and clinical research and development of a related synthetic compound into the novel cancer drug Eribulin. 

A variety of technology transfer methods were put in place to facilitate involvement of the parties necessary to bring halichondrin B to market and to overcome various obstacles that were encountered along the way. After halichondrin B was isolated by Japanese scientists from Eisai Inc. in 1986, NCI accepted the compound for initial preclinical testing and made it the original test case for the NCI 60 cell line screen. During this testing, halichondrin B’s unique mechanism of action as a microtubule destabilizer was elucidated. 

After realizing the compound had tremendous potential as an anticancer agent, NCI prioritized its development and began to explore methods to generate sufficient quantities for further preclinical and clinical testing. A Letter of Collection (LOC) was put into place between NCI and the New Zealand government to harvest the species of sponge that yields halichondrin B. After discovering that one metric ton of sponges would only yield 300 mg of the compound, it became clear that the development of synthetic analogs would be the most viable option for further development of the compound. Supported by grants from NCI, Harvard researchers developed synthetic methods and licensed the synthetic methodologies and patents to Eisai, who subsequently developed many synthetic analogues to halichondrin B. 

Eisai then negotiated a screening Material Transfer Agreement (MTA) with NCI under which NCI performed studies comparing the anticancer activity of the synthetic analogues with that of the parent compound. These studies demonstrated that the synthetic analogs were as safe and effective as the parent and provided strong rational for the product’s continued development. In 2004, Eisai and NCI entered into a Clinical Trials Cooperative Research and Development Agreement (CRADA) to finalize preclinical studies and initiate early phase 1 clinical trials to evaluate the safety of the synthetic analog in patients with cancer. These studies resulted in FDA priority approval of Eribulin on November 15, 2010 for the treatment of patients with metastatic breast cancer. This technology transfer effort has been of critical importance as there are limited treatment options for women with aggressive forms of late-stage breast cancer who have already received other therapies. The CRADA term was extended and the parties currently have plans to explore development of the synthetic analog of halichondrin B for treatment of other types of tumors. 

Awardees

NIH - National Cancer Institute

• Dr. Sherry Ansher
• Dr. David Newman