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GSK Abandons Resveratrol, Focuses on Next Generation Compounds

GlaxoSmithKline has reportedly abandoned work on SRT501, or resveratrol, the controversial drug based on the ingredient found in red wine that has been said to reverse the aging process. The news came as no real surprise—the company has been quiet about the compound since May, when it halted a clinical trial of the drug in multiple myeloma after cases of kidney failure occurred. (find background on that news and other controversies around the drug herehere, and here.). But confirmation that SRT501 is officially done for is prompting many to wonder about what else Sirtris has up its sleeve—specifically, what exactly is going on with the follow-on compounds it has put in the clinic. The news is also reinvigorating a debate over the value of Sirtris. As you’ll recall, GSK paid $720 million for Sirtris in 2008, and industry folk have been questioning the hefty price tag ever since.

Just before Thanksgiving, GSK had a group of reporters into the Sirtris offices to provide an overview of its externalization strategy for R&D. Given the very public debate over the value of its technology, it was an interesting choice of venue. But their offices were spacious, and we got a tour of their labs, which house about 70 people who operate fairly autonomously from the overall GSK operation. I can attest that there were indeed chemists in lab coats makin’ compounds while I was there.

The day included a presentation by George Vlasuk, former vice president of metabolic disease and hemophelia research at Wyeth who last year came over to GSK to lead Sirtris. He was brought on to keep pursuing “the dream,” of resveratrol, “but do it in a slightly different way,” Vlasuk said. Prior to GSK’s purchase of Sirtris, “the science, in some regards, didn’t get as fully elaborated as it could have,” he acknowledged.  His job was to “make sure the science was solid and we were going down a path you could really develop drugs from.

From the presentation, it was clear that work on SRT501 was dead in the water, as the focus of Vlasuk’s talk was squarely on the next set of compounds. Sirtris has developed a library of over 6,000 molecules that turn on SIRT1, the target of resveratrol, that are chemically unrelated to resveratrol, Vlasuk said. The company also recently published a paper on SIRT1 modulation, which can be found here.

The first molecules to come out of that work are SRT2104 and SRT2379. Sirtris is wrapping up a series of clinical trials of those compounds and plans to discuss results from those early-stage studies in the first half of next year, he said.

As for SRT2104, Vlasuk noted that it “has some very profound effects on metabolism in an animal that represents an obese, metabolically challenged disease state.” In other words, it seems to be causing weight loss in animal models. Further, he added, that weight loss was not linked to eating less, rather to enabling the animal to use energy more efficiently. The finding is “very critical” because the compound is being developed for diabetes. “The next generation of diabetes medicines are going to be focused on compounds that utilize energy,” he said.

That’s all well and good, but Sirtris appears to be many years off from putting either of its two lead compounds into an advanced trial. Vlasuk acknowledged that the delay was because the company might have to deal with potential downside of activating Sirt1. The enzyme is believed to play a critical role in many pathways, making tweaking it rife with potential side effects. Those downsides would be particularly necessary to sort out if the drug is being developed for a chronic disease, like diabetes.

One tidbit worth noting was that Wyeth was the first big pharma to invite Sirtris in to present its technology. Vlasuk tried to get Wyeth management to do a deal with Sirtris back in 2005, but they weren’t convinced it was worthwhile. “Glaxo saw the light,” he said. Whether anyone will continue to believe in Sirtris now that resveratrol has been snuffed out remains to be seen.

3 Comments

  • Dec 1st 201020:12
    by Bill Sardi

    What happened to the fascinating idea of an anti-aging pill? OK, they have molecules that rev up metabolism and deal with metabolic syndrome — that makes it a drug. Not sure an anti-aging pill can ever be a drug because of its high price. An anti-aging pill would be for the masses (can’t imagine the problem of only the wealthy affording such a pill if it materialized). Tne French have more centenarians per capita than any other country, which is attributed to their consumption of red wine. Roger Corder of the William Harvey Research Institute in the UK, and author of the WINE DIET, believes it is the total polyphenols, not just resveratrol, that is responsible for the lower mortality rates among wine drinkers. There is only 1 mg of resveratrol at best in a 5-oz glass of red wine. But there are 60 mg of total polyphenols. 3-to-5 glasses is the optimal health intake range, providing 180-300 mg polyphenols. Remove the alcohol and consolidate the red wine solids into a pill and it should confer longevity, maybe even better and certainly safer than wine.

  • Dec 5th 201020:12
    by anon

    “In other words, it seems to be causing weight loss in animal models. Further, he added, that weight loss was not linked to eating less, rather to enabling the animal to use energy more efficiently.”

    This is wrong. A pill that does not decrease food intake and increases energy efficiency will cause weight gain. Think about it.

    Good to see more stellar science coming from Sirtris.

  • Dec 16th 201018:12
    by Robert L Shirley, M.D.

    Robert Casper from Toronto has shown that resveratrol blocks the human cell- receptor for dioxin … while working on his sabatical in Paris. Does SK know this?

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