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 here, here, 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...

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Post-BIO News Roundup

Been focusing on Chicago and this year’s BIO extravaganza all week? Here’s a sampling of news you might have missed. Pirfenidone rejected In a surprisingly twist, FDA refused to approve InterMune’s lung treatment pirfenidone, despite a positive recommendation from its advisory committee. The agency wants another lengthy trial to better demonstrate pirfenidone is effective at treating idiopathic pulmonary fibrosis, a debilitating and ultimately fatal lung disease for which there are no approved treatments in the U.S. or Europe. InterMune’s stock fell over 75% on the news. Check out this piece in Forbes’ health care blog on whether FDA is these days less likely to listen to its advisory panels. Birth Control Pill Exalted The mainstream media celebrated as “The Pill” turned 50. Technically, they’re celebrating the 50th anniversary of its approval by FDA. C&EN covered the chemistry story of the pill in “The Top Pharmaceuticals That Changed The World” special issue, back in 2005. Don’t miss the classy 1950s era photo of Carl Djerassi. Resveratrol Trial Halted A GlaxoSmithKline clinical trial studying a reformulated version of resveratrol was suspended on April 22 due to safety concerns, but company officials say the complications may or may not be related to the drug. The big question remains-what does this all mean for the effort to make drugs out of resveratrol, the trace component of red wine that’s been touted as a cancer fighter and a fountain of youth in a bottle? Resveratrol research has been in the spotlight a lot lately, not just for good reasons. GSK got the reformulated resveratrol (also called SRT-501) when it acquired biotech company Sirtris in 2008, to the tune of $720 million. Sirtris based its business around evidence that resveratrol turned on enzymes called sirtuins. The belief was that this activity could underlie some of resveratrol’s beneficial effects. Sirtris developed other drug candidates based on this idea that the company says look nothing like resveratrol, and some of those entitites are in clinical trials as well. But the sirtuin connection has been called into question on multiple occasions. And now, with news that some patients in the resveratrol clinical trial developed cast nephropathy, a condition that can lead to kidney failure, the Wall Street Journal Health Blog is wondering aloud whether resveratrol’s 15 minutes of pharmaceutical fame are coming to an end. GlaxoSmithKline officials say they are studying the data further, and that they stopped the trial “out of an abundance of caution”, according to the Wall Street Journal. The trial was conducted in patients with multiple myeloma, and apparently, cast nephropathy is common in myeloma patients. Commenters at “In the Pipeline” (which, by the...

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