Comments on the Sirtris Acquisition
Sirtris Pharmaceuticals is something of a figurehead for the resources flowing into calorie restriction research at all levels over the past few years. As I'm sure you saw in the media, Sitris was recently acquired by GlaxoSmithKline for a fair chunk of change; in an age of oppressive regulation and the enormous investment in time and money required to satisfy that regulation, this is the preferred exit strategy for investors, as it's the only one likely to happen rapidly. Some thoughts from those who watch the industry below:
Sirtris to be acquired by GlaxoSmithKline:
Sirtris has focused on the commercial development of clinically useful sirtuin activators, which are predicted to be useful as anti-diabetic drugs. Data from academic labs have suggested they could be of even wider use, e.g., in increasing exercise tolerance or treating inflammatory disease. Underneath it all, of course, is the knowledge that the the sirtuins were initially identified as longevity assurance genes; the subtext of all discussions of sirtuin activators is that they may mediate their beneficial effects by slowing aspects of the aging process itself.
The acquisition of an small company at a large premium (the offer was more than 80% higher than Sirtris' market cap) by a pharmaceutical giant is one of the first demonstrations that the drug industry is taking seriously the idea that there's money to be made in treating aging per se rather than all of the associated conditions separately
Sirtris, as you'll recall, is centered on the exploration and manipulation of sirtuins such as SIRT1. Ouroboros also provides an overview of what is presently known about the role of SIRT1.
$720 Million Worth of Sirtuin Research:
Of course, Sirtris hasn’t officially been targeting life extension drugs, at least not in the near term. A number of these potential life-extending biochemical pathways are tied up with insulin signaling, which makes sirtuin-targeted drugs a natural for diabetic therapy as well. Sirtris has reported encouraging data for just that indication. If a sirtuin-based drug is going to make it to market, that’s a good bet for how it’ll do it. ... Once one of these drugs is approved, it’ll have the biggest, strangest potential for off-label use that anyone has ever seen. Oh, that’s going to be something to watch. GSK is well aware of this - I’m not saying that it’s part of their business plan, but when you see their head of drug discovery talking to Forbes and tossing the word "transformational" around, you know that they’ve thought beyond a replacement for Avandia.
That’s the truth, all right, and it’s going to be fascinating to watch things develop. As I was saying here the other day, a drug for aging is a perfect example of something the FDA has absolutely no idea of how to approach. Well, it’s not just the FDA, come to think of it: how on earth would you design a Phase II trial for life extension? How long would it take? What’s your clinical endpoint? And further on, how long will you want to monitor your Phase III patients (recall Pfizer’s recent follow-up of Exubera trial participants? How long will it take before you could be sure that some horrible bargain wasn’t struck along the way?
Notice that the largest problem for the future of longevity medicine in the established research and development community is the FDA and its heavy-duty, risk averse structure of trials after trials after trials. The cost is immense, and in most cases utterly out of proportion to any rational cost-benefit analysis of a new medical technology. So those technologies simply aren't commercialized, joining the vast sea of wasted potential that attends all imposition of regulatory cost.
The simple answer to the questions in the quote above is that you don't run a Phase II trial for life extension strategies. It doesn't make sense to talk about these structures and strategies rigidly applied to this case, but the present weight of regulation doesn't allow for the sort of free competition and innovation under pressure that always produces working, practical answers.
Since the FDA will never approve an intervention into the aging process - as aging is not recognized as a disease, and the FDA only approves treatments for disease - the underlying technologies are not applied to that end. No-one invests in medicine that cannot be sold due to government prohibition. Instead, the promising science is diverted into the same old process of patching up the very end results of age-related damage. It's that simple and that wasteful.
Absent a very overdue revolution, change to this sorry state of affairs will be slow and expensive, a matter of lining the pockets of politicians to re-order some of the destruction they've caused. A part of that long change process is the assimilation of potential new longevity science into organizations large enough to influence the FDA's mandate. Here, we see one of the first acts in that play.
I'm not convinced that there's anything wrong with the FDA approval process per se. As complicated and lengthy as it is, it still fails in dramatic ways (e.g. Vioxx). Nonetheless, your point about longevity treatments still stands. There needs to be some sort of opt-out (i.e. a covenant not to sue the prescribing doctor, dispensing pharmacy, pharmaceutical manufacturer, or anyone else involved) for people who want to use drugs off-label and are willing to accept the risks.