China experiences diabetes epidemic

SHANGHAI, China—Thirty years ago, the people of China had noreason to worry about diabetes. But add a cultural revolution, Western ads,fast-food chains and sprawling supermarkets to the mix, and you've got therecipe for an obesity epidemic thriving in the once-ancient land oft plagued byfamine.

In fact, China has now surpassed America in diabetes cases.In the United States, diabetes affects 25 million people, compared to 92million in China and 230 million worldwide, the New England Journal of Medicine reports. Characterized by chronichigh blood-glucose levels, diabetes, if left untreated, can eventually lead tolong-term complications including cardiovascular disease, chronic renalfailure, blindness and strokes.

With this in mind, Hua Medicine, the leading drugdevelopment and commercialization company in China, and Basel,Switzerland-based Roche recently signed a licensing agreement for Roche'sglucokinase activator (GKA) program. GKA is a novel, small-molecule activatorof the glucokinase enzyme that plays a key role in regulating carbohydratemetabolism. By increasing this enzyme's activity, GKA has the potential to helplower elevated blood-glucose levels seen in diabetes, according to Roche.

Roche first demonstrated efficacy in lowering blood-glucoselevels of diabetic patients in clinical trials using a previous generation ofits GKA compounds. The current and most advanced generation of the GKA drugcandidate that is being licensed by Hua has been further optimized for safetyand efficacy and is now ready to begin clinical studies.

Under the agreement, Hua Medicine will receive the fullpreclinical and clinical documentation for Roche's GKA program, the drugproduct API for RO5305552 and rights to potential back-up compounds. In return,Roche will receive an upfront payment, milestones and royalties. Hua Medicinehas also been granted the exclusive development, manufacturing and worldwidesales and marketing rights with the rights to sublicense.

"Roche's GKA was designed to be a best-in-class drugcandidate based on their extensive preclinical, clinical and mechanisticexperience with GK activation," says Li Chen, CEO of Hua Medicine. "We are veryexcited to extend the outstanding scientific efforts initiated by Roche and tobe granted the opportunity to carry forward the clinical development of GKA.Our ultimate goal is to materialize the potential of GKA to help millions ofpatients suffering from diabetes in China and worldwide.

"Hua is focused on building a new and better way to developand commercialize drugs, leveraging the best of what the Eastern and Westernworlds have to offer," Chen continues. "We are fortunate to have a strong teamthat extends to a prominent group of healthcare investors, including newcorporate investor, Wuxi PharmaTech, the entrepreneurial leader in China'slife-science sector."

Hua Medicine and Roche are natural partners, says Stella Xu,executive director of Roche Partnering Asia.

"Hua is led by Dr. Li Chen, a former Roche employee, who ledthe preclinical development work of the GKA compound in China before he startedHua with strong VC funding," Xu tells ddn."Hua and Roche share the same focus on science and aspiration to quicklydevelop this project and address the growing unmet medical needs in China andworldwide for diabetes.

"Though Hua is a young start-up, it is well funded and hasan experienced managed team and investors to further develop this compound," Xuadds. "We hope Hua can move this project forward efficiently and effectively.Hua is a good example of the new generation of Chinese biotechs that iscommitted to innovative pharmaceutical R&D. We also hope to use thisopportunity to further support such innovation-based biotech industry inChina."

Hua has licensed the commercial rights to market GKA fromRoche, says Xu, who adds that the company does not disclose financial details.

Chen plans to file a clinical trial application in China inMarch or April, with hope to launch Phase I trials by the end of the next yearin China, and to complete Phase II trials by 2015.

However, Hua faces some competition. Eli Lilly & Co. hasa GKA in Phase II. LY2409021 was obtained through a licensing deal with OSIPharmaceuticals (now Astellas Pharma Inc.) in 2007, according to news reports.Forest Laboratories Inc. is also in the mix, with GK1-399, obtained fromTransTech Pharma Inc. in 2010, in Phase I. As China becomes a growing economicforce, biotech firms, pharmaceuticals and the healthcare industry feel a senseof urgency to come up with a novel drug to deter obesity and its closecompanion, diabetes.

Evolution of diabetesepidemic in China

According to Barry M. Popkin, a professor of nutrition atthe Carolina Population Center, University of North Carolina in Chapel Hill,"the rate of obesity in China has accelerated during the past decade and couldeasily double over the next two decades."

"Rapid social and economic change is transforming China,with enormous implications

for its population and economy," Popkin wrote in Disease & Demography in itsJuly/August 2008 issue. "More than a fifth of China's adult population isoverweight, which is related to changing dietary and physical activitypatterns. The related economic costs represent four to eight percent of theeconomy. Public investments are needed to head off a huge increase in themorbidity, disability, absenteeism and medical care costs linked with thisnutritional shift."

The stage was set for this dilemma since 1985, when "rapideconomic growth and a remarkable shift in the diet structure have led to theobesity epidemic," Popkin wrote.

Soybean oil has also been a major culprit in the war againstcalories since 1990 and 1991, when major changes in Chinese tax and importregulations led to the rapid increase in the dietary intake of oils—both in thelarge amount of soybean oil consumed and vegetable oils—many containing highlypathogenic products, Popkin said.

Intake of edible oil in China almost doubled between 1989and 1991, as per-capita intake increased from 23.2 to 41.6 grams per day amongadults, Popkin stated. The consumption of eggs, poultry, beef and pork has alsoincreased rapidly in China, and milk intake has recently begun to risereflecting that for each additional increase in income, China's adults proportionallyincrease their intake of animal-source foods.

And while China likes fast food and soda, it is the conceptof the rows and shelves of food in the supersized grocery store that is mostappealing as China experiences "the world's fastest growth in supermarkets,especially superstores such as Wal-Mart with sales growing by as much as 40percent annually," he said. "By 2003, more than $55 billion had been spent onconstruction of supermarkets."

"The classical Chinese diet—rich in vegetables and carbohydrateswith minimal animal source food—no longer exists," Popkin said. "In 2006, fewerthan 1 percent of all Chinese adults consumed a diet with less than 10 percentof energy derived from fat. Overweight status in China among adult malestripled and among adult females, doubled, between 1989 and 2000. By 2004,nearly a quarter of all Chinese adults were overweight."

Forest Laboratories Inc.

http://www.frx.com/

TransTech Pharma Inc.http://www.ttpharma.com/

Carolina Population Center

http://www.cpc.unc.edu/

University of North Carolina