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.

Halichondrin B is a compound isolated from a species of marine sponge, used for preclinical and clinical research and development of a related synthetic compound into the novel cancer drug Eribulin.

After halichondrin B was isolated by Japanese scientists from Eisai, Inc. in 1986, the National Cancer Institute (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 demonstrated.

Realizing the compound had tremendous potential as an anti-cancer agent, NCI began to explore methods to generate sufficient quantities for further preclinical and clinical testing. A Letter of Collection was put into place between NCI and the New Zealand government to harvest the species of sponge that yields halichondrin B.

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.

After discovering that one metric ton of sponges would yield only 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, which subsequently developed many synthetic analogs to halichondrin B.

Studies demonstrated that the synthetic analogs were as safe and effective as the parent and provided strong rationale for the product’s continued development. In 2004, Eisai and NCI entered into a clinical trials Cooperative Research and Development Agreement (CRADA) to finalize pre-clinical studies and initiate early phase 1 clinical trials in patients with cancer.

These studies resulted in FDA priority approval of Eribulin in 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.