HZI Molecule Transformed into a Cancer Medicine in the United States

Balling: Colossal Success for Biomedical Research in Germany


The pharmaceutical company Bristol-Myers Squibb (BMS) recently obtained approval in the American market for IXEMPRA, a semi-synthetic analog of epothilone B, for the treatment of patients with metastatic breast cancer resistant or refractory to anthracyclines, taxanes, and capecitabine.  The epothilones were originally discovered and researched by scientists at the Helmholtz Center for Infection Research in Braunschweig, Germany.  Bristol-Myers Squibb licensed epothilone technology in 1997 from the Helmholtz Center.  Physicians in the United States will be able to immediately use IXEMPRA, the semi-synthetic epitholone B analog, to treat patients.  Pharmaceutical experts think Ixempra has a great potential as a breast cancer medicine – and later for other types of cancer.  It is anticipated for European licensing in the second half of 2008.  

The team of scientists with the chemist Prof. Gerhard Höfle and the biologist Prof. Hans Reichenbach at the former Society for Biotechnological Research (now under the name of the Helmholtz Center for Infection Research) discovered epothilones as early as in the 80’s. This new class of biologically active natural substances comes from the myxobacteria living in the soil. Epothilones act on what are known as microtubuli in body cells. The microscopically tiny tubes distribute the chromosomes (the media of genetic information) to the daughter cells during cell division. When epothilones come into the cell, they block the microtubuli and the cells cannot divide. Then they die off and are decomposed. Since cancer cells divide particularly frequently, they react very sensitively to epothilone. The result is a deceleration in tumor growth so that tumors shrink and disappear.

The first step in the process of development was the observation of the microbiologist Dr. Klaus Gerth from Reichenbach’s team that a special strain of a type of myxobacteria produces an interesting substance that can kill off living cells. Dr. Norbert Bedorf from Höfle’s natural substance chemistry department produced this substance in pure form for the first time and resolved its chemical structure. That was when epothilone entered the stage of pharmaceutical research.

Then, there followed more years of intensive research because they not only had to enhance the chemical structure, but also improve epothilone production. This is the reason why the myxobacteria were genetically modified to produce new bacteria that could generate sufficient quantities of the epothilones for potential cancer agent. Secondly, the scientists had to create the best conditions for life in bioreactors for the high-performance bacteria bred in this fashion. Finally, this production process was used as a basis for manufacturing the medicine. Bristol-Myers Squibb then developed a semi-synthethic version of epothilone B and conducted the necessary preclinical studies and later global clinical trials with patients in order to apply for a license.

There was great satisfaction with these findings, as Prof. Dr. Rudi Balling, the scientific director of the Helmholtz Center, expressed: “Epothilone proves that public biomedical research in Germany is world class and it can come up with answers to the urgent health problems of humanity. It was the Helmholtz Society that combined high-profile pure research with the perspective of industrial applications.” But, as the success story of epothilone shows, you need a lot of patience.

And that, along with scientific creativity, was Höfle’s and Reichenbach’s key to success. “We are extremely proud of the role of our co-workers in helping to develop this new class of cancer therapy and harvesting the fruits of 30 years of biological and chemical research work.”