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New cancer treatment drug enabled by UC research

The New Zealand
Lissodendoryx sponge, the natural source of halichondrin B
– the active compound used to underpin the newly-approved
breast cancer treatment drug Halaven.
The New Zealand Lissodendoryx sponge, the natural source of halichondrin B – the active compound used to underpin the newly-approved breast cancer treatment drug Halaven.

Development and release of new cancer treatment drug enabled by UC research

The development and release on November 15 of the new cancer treatment drug Halaven by USA company Eisai Inc., would not have happened without the input of University of Canterbury researchers.

“Without the New Zealand material and the work done in New Zealand, none of the future development would have occurred,” said Dr David Newman, Chief of the Natural Products Branch at the USA’s National Cancer Institute.

Dr Newman organised the New Zealand supply contract for the natural product halichondrin B, isolated from a deep-water marine sponge off Kaikoura, which was used in underpinning the development of the drug that was released last month.

This supply of halichondrin B to the NCI was just part of a large effort by University of Canterbury chemists, doctoral and postdoctoral researchers since 1983. These efforts have been directed by Emeritus Professors of Chemistry at the University of Canterbury, John Blunt and Murray Munro who say that it is very gratifying to see the study of natural products at UC contributing to the release of a drug that will greatly assist cancer patients around the world.

“This release to market of Halaven is another example of the value of the study of natural products in the development of drugs for human and animal use. Halaven is currently approved for use for the treatment of refractory breast cancer but its makers have said that it is likely to command a US$1-billion per year market when it is approved for treatment of other cancers.”

Initial work undertaken by UC postdoctoral researcher Dr Rob Lake in the mid 1980s identified a sponge sample that yielded an extract with what is described as “exquisitely potent activity” against cultured cancer cells. In an animal model it provided a remarkable life extension of 250 per cent. In 1988 Dr Lake went on to identify the active compound as halichondrin B which had very recently been identified by Japanese workers and then from US researchers from different sponges.

Dr Lake’s work was published in 1994 after further work at UC by postdoctoral researcher Marc Litaudon and PhD researcher Jo Hart identified a new version of the halichondrin, isohomohalichondrin B.

“The USA’s National Cancer Institute was very interested in obtaining a large supply of halichondrin B to extend studies they had initiated which indicated a novel mode of action for this compound in arresting the growth of tumour cells. The yields of this compound from the Japanese and US collections of sponges were extremely small, whereas the New Zealand Lissodendoryx sponge had a ten-fold better return.

“The NCI then organised a contract with the University of Canterbury group to supply much larger quantities of the halichondrin B. Following surveys conducted by UC postdoctoral alumnus Dr Chris Battershill at NIWA, approval was given by the New Zealand Government for the collection of 1,000 kg of the sponge by deepwater dredging off the coast of Kaikoura.

“Extraction of the sponge was carried out by Dr Stephen van Eyk at NZ Pharmaceuticals in Palmerston North. Dr van Eyk and New Zealand Pharmaceuticals’ then CEO Dr Richard Garland and Manager Dr Selwyn Yorke are all UC chemistry graduates.

“Final purification of 310 mg of halichondrin B was achieved at the UC by Sarah Hickford. This supply to the NCI enabled them to carry out xenograft experiments in mice, the early results of which caught the attention of the Eisai Company in 1998. Head to head comparisons, in the NCI xenograft experiments, of the New Zealand-supplied halichondrin B with some synthetic analogues of the halichondrin that Professor Kishi (Harvard University) and Eisai had prepared showed that one of the Eisai compounds was quite superior to the natural product. Eisai were about to discontinue their development of the synthetic compound, but these experiments encouraged them to continue with the project. Following extensive clinical trials by Eisai, some in collaboration with the NCI, the US FDA finally gave approval for the release of Halaven in November.

“Without research undertaken at the University of Canterbury this new drug would not have been developed further and would not have made it the market. We can be proud of the many UC researchers and alumni over the past 25 years who have contributed to this outcome.”


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