January 26, 2010

USA: Doubts Build On Glaxo's Antiaging Drugs

. NEW YORK, NY / Forbes.com / Business / Pharma & Health / January 26, 2010 By Matthew Herper GlaxoSmithKline shocked the pharmaceutical industry in 2008 when it dropped $720 million to buy Sirtris Pharmaceuticals, a biotechnology company working on drugs based on resveratrol, a chemical in red wine thought to combat the effects of aging. The drugs are thought to enhance the activity of SIRT1, a key enzyme involved with the aging process. Glaxo hopes the drugs will lead to myriad new treatments for diabetes, cancer and other diseases. But now researchers at rival companies are openly questioning whether the compounds will work. They say they are unable to replicate key laboratory experiments backing the drugs' promise. In the latest salvo, Pfizer researchers report in the January Journal of Biological Chemistry that neither resveratrol nor several other Sirtris drugs hit the SIRT1 enzyme at all. They suggest that Sirtris' earlier findings to the contrary might be due to an experimental artifact. The Pfizer study follows on the heels of similar study last year from researchers at Amgen. In 2007 Sirtris made headlines when it reported that a compound called SRT1720 lowered blood sugar in diabetic mice. But when Pfizer researchers tried to repeat the experiment, they found that low doses of SRT1720 had no effect on blood sugar whatsoever--and the mice gained weight. High doses of the drug, meanwhile, killed three of eight mice, the Pfizer study says. Sirtris has generated mountains of hype over the years. Its cofounder, Harvard biologist David Sinclair, had published studies showing evidence that large doses of the resveratrol chemical in red wine extends the lives of fat mice. Breathless press coverage has hinted that the compound, or its successors, could one day become life-extending pills for humans. Sirtris' raison d'etre was to create more potent versions that could combat myriad diseases of aging. Photo credit: expressnews.ualberta.ca The Pfizer scientists "have thrown down the gauntlet: They claim that the reported Sirtris compounds do not do what they are claimed to do," pharmaceutical chemist Derek Lowe, wrote recently on his popular In The Pipeline blog. It is "almost certainly the case" that there are problems with the Sirtris compounds, he argues. In an interview, Glaxo's chief executive says his company's approach has always been "much more subtle" than "this very simplistic notion of this as a longevity pill." He calls the dustup "a bit of a storm in a teacup" and says the drugs Pfizer tested in animals are not the same ones that Glaxo is currently testing in people as possible diabetes or cancer treatments. "We're not at all surprised that there's some controversy," says Witty. "Because there always is. People always have different opinions. Frankly, we didn't think what was published was particularly comprehensive. We feel good about where we stand today." Witty says he's comfortable with paying for high-risk research that may not always pan out. This focus on unpopular approaches has been a key part of Witty's attempts to revive Glaxo's research. Like those of every drug company, Glaxo's labs have been relatively fallow for years. Already, the unpopular thinking has paid off. Wall Street expected a lupus drug Glaxo was developing with Human Genome Sciences to fail. Instead it is likely to be one of the biggest-selling new medicines launched this year. Other risky bets include a drug that aims to prevent heart attacks by combating artery inflammation, and a partnership with Anacor, a San Francisco company that makes drugs based on a new type of chemistry involving the element boron. Witty says that researchers at Glaxo thought it was "completely mad" to do the Anacor deal. "There's no doubt there's risk in pharmaceuticals, and there should be!" Witty says. "If you make 30% returns it should be a risky business. If you don't want risk, go be a grocery store and make 6%." [rc] 2010 Forbes.com LLC™