Glaxo Gives Up On Its Fountain Of Youth Pill
4 CommentsBy Ed Silverman // December 3rd, 2010 // 8:51 am
And so, $720 million later, GlaxoSmithKline has finally discontinued work SRT501, a drug designed to mimic the anti-aging benefits of red wine, saying the compound did not work sufficiently in advanced multiple myeloma patients and caused kidney damage. This is not terribly surprising, given that a clinical trial was halted last spring for ‘unexpected safety events’ (see here).
The discontinuation is a bit of an embarassment for Glaxo. Earlier this year, there was quite a flap over the value of the Sirtris compound. Sirtris, you may recall, made a name for itself by developing drugs that activate sirtuins, a class of enzymes involved in aging, and its most advanced compound was a formulation of resveratrol, a substance found in red wine and plants. Lured by the fountain of youth, Glaxo two years ago shelled out a fair amount of money for SRT501 and a couple of other compounds.
However, two different groups of scientists from other drugmakers - first, Amgen and then Pfizer - in the past year published articles questioning the notion that such compounds can directly boost an enzyme that slows down the aging process (see this and this). In hopes of salvaging its $720 million payout, Glaxo is now focusing on two “more selective SIRT1 activator compounds that have no chemical relationship to SRT501 and more favorable drug-like properties,” a Glaxo spokeswoman writes us.
This is not the first time the Sirtris deal has humiliated Glaxo. A few months ago, two key Sirtris execs who assumed important roles within Glaxo’s hiearchy - Michelle Dipp and Christoph Westphal - joined a non-profit called the Healthy Lifespan Institute to sell resveratrol supplements online. Although this was a different formulation, Glaxo didn’t know about the online sales. Both were forced to resign from the non-profit board (back story).
In any event, drugs that fail in the lab are, well, an age-old story.
industry insider
GSK needs such a pill to rejuvenate its fortunes.
Ethical Monitor
GSK needs to rejuvenate its pipeline. Their habit of trying to make inexpensive dietary supplements like Omega 3 (Lovaza) and natural food enzymes expensive prescription products is not going to help the patients who need them. Maybe they should look at ginko biloba for improving brain power.
When I worked for GSK I was driven to drinking the whole bottle of wine - but I still aged 10 years in 14 months.
Ronda Harrison
SRT501is a synthetic form of the molecule produced either by fermentation or organic chemical engineering. It is not pure resveratrol at all. It is complexed with another material, probably cyclodextrin, to make it more water soluble. Synthetic resveratrol sometimes contains either remnants of the bacteria or yeast which has been modified to produce the molecule or other, what are known as, “unknowns” which show up on an HPLC fingerprint of the molecule. Some researchers have reported instances of mild toxicity associated with synthetic resveratrol. I do not believe that there are any reports of such toxicity related to natural resveratrol.
If there are any lessons here at all regarding resveratrolit they are to:
1. avoid synthetic resveratrol, or any complex of resveratrol with cyclodextrin or Tween (another solubility agent) and
2. Stay away from micronized resveratrol. There is no evidence that it is effective.
Dr Susanne Fleming
As I see it the dilemma for Glaxo, was always that the Sirt activation products they are developing already exist in safe effective natural, inexpensive form. Given, Glaxo’s synthetic analogs may be more potent or more precisely targeted against specific metabolic pathways and transcription factors, but there exist other stilbenes such as pterostilbene with superior such properties. Biotivia transmax, the concentrated resveratrol being used in the human trials at Albert Einstein Med Ctr. and a number of other medical schools, has been extensively tested and shown to be non toxic even at a high dose and is available now, not five to seven years from now which is normal for new pharmaceuticals. Synthetic analogs historically have been shown to be somewhat unpredictable in effect and safety. Why not simply stick with the natural form? To succeed from this point forward Glaxo will have to come up with sythetic versions of resveratrol that are shown to be clearly superior to resveratrol itself and just as safe. So far this has not happened.