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Kidney Disease Drug With Cancer Center Origins Licensed in Asia

January 22, 2010
Lebanon, NH

Drs. Sporn & Libby

Michael B Sporn, MD, and Karen Liby, MD

Thanks in part to more than a decade of preclinical work by Cancer Center researchers, a Japanese biopharmaceutical firm is preparing to develop and market throughout Asia a drug for the treatment of chronic kidney disease (CKD).

In a deal worth $272 million plus royalties, the firm Kyowa Hakko Kirin bought exclusive rights to the compound bardoxolone methyl-or CDDO-methyl ester (CDDO-Me), in the scientific literature-from Texas-based Reata Pharmaceuticals on Thursday, January 7. The drug belongs to a family of anti-inflammatory compounds called triterpenoids, which chemist Tadashi Honda, PhD, began synthesizing at the Dartmouth laboratory of Gordon Gribble, PhD, in 1995. Since then, Cancer Center Cancer Epidemiology and Chemoprevention Research Program member Michael B. Sporn, MD, and his lab team have been testing them for bioactivity.

Sporn and members of his lab, including co-investigator Karen Liby, PhD, found in animal trials that synthetic triterpenoids simultaneously inhibit many kinds of tumor cells, suppress inflammation, and protect healthy, non-cancerous cells. While focusing on cancer prevention and treatment, the researchers found that the anti-inflammatory, anti-oxidant, and cyto-protective properties of triterpenoids also can apply to a wide range of inflammation-related diseases. These conditions include diseases of the kidney, the heart, the respiratory system, and the central-nervous system.

Triterpenoids "are not anti-oxidants themselves," explains Sporn, Dartmouth Medical School Professor of Pharmacology and of Medicine. "They turn on the body's own anti-oxidant defenses, which is most important."

Following up on the Sporn lab's cancer research, collaborators at Cornell reported that in tests on rodents, one of the triterpenoids appears to help in preventing such neurodegenerative diseases as Parkinson's, Alzheimer's, and Huntington's.

After securing patent protection for the CDDO-Me compounds, Dartmouth College's Technology Transfer Office (TTO) identified Reata as a private-sector collaborator for further development. Under a licensing agreement with Dartmouth, Reata has been conducting human trials with the compounds.

In announcing the deal with Kyowa, Reata reported that "in two Phase 2 trials, bardoxolone significantly improved renal function in Type-2 diabetic patients with advanced CKD. ... Significant improvements were also seen in other markers of renal function, [control of blood-sugar levels], and cardiovascular disease."

The agreement gives Kyowa exclusive rights to develop and sell bardoxolone for CKD and related conditions in Japan, China, Taiwan, Korea, and southeast Asia. Reata retains the rights to develop and sell the drug in the United States, Europe, Latin America, and Asian markets beyond Kyowa's territory.

According to Alla Kan, TTO director, the Reata/Kyowa agreement "provides a wonderful opportunity for Dartmouth to bring the fruits of our research to patients. This is a most exciting development and a vivid illustration of academic research transfer to industry for the benefit of humanity."

Sporn, considered "the father of chemoprevention" for his pioneering use of medications to fend off cancer and other diseases, hails the agreement as the culmination of a new drug going "'all the way' at Dartmouth, from conception, to synthesis, to preclinical development, and then to final licensing to a pharmaceutical company for clinical development."

Sporn also praises the work of his collaborators, paricularly Liby and her experiments with mice. "This woman has a unique talent for doing research," Sporn says.

More Information on the Sporn Lab's Work on Triterpenoids

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