Innovation?

It's no secret that pharmaceutical companies spend a large amount of money on promotion and marketing of their products, but the amount going into research and development is not insignificant (2004 US estimate of over $24 billion in R&D expenditures). But how much of that R&D money translates into innovative new products or improvements on current therapeutics?

The French publication Prescrire (link to English site) provides an annual report on new drugs released in France and rates them based on therapeutic advance and risk-benefit balance. In 2010, they reviewed 97 new drugs and indications, but first the rating system:

Bravo: The product is a major therapeutic advance in an area where previously no treatment was available.

A Real Advance: The product is an important therapeutic innovation but has certain limitations.

Offers an Advantage: The product has some value but does not fundamentally change the present therapeutic practice.

Possibly Helpful: The product has minimal additional value, and should not change prescribing habits except in rare circumstances.

Nothing New: The product may be a new substance but is superfluous because it does not add to the clinical possibilties offered by previous products available. In most cases it concerns a me-too product.

Judgement Reserved: The editors postpone their rating until better data and a more thorough evaluation of the drug are available.

Not Acceptable: Product without evident benefit but with potential or real disadvantages.

The review includes new products (other than generics copies) and new indications proposed by drug companies as well as new dose strengths and new form/presentations of existing drugs. Results from the past 10 years can be found here including the 2010 data reproduced below:


In 2010, over half the new products or indications added nothing new to existing clinical possibilities and almost 20% had potential or real disadvantages over current practice. The lone real advance was imatinib (Gleevec) reassessed in inoperable or metastatic gastrointestinal stromal tumours.

While breakthrough drugs might be expected to be relatively rare (only 2 in the last 10 years by Prescrire's account), the fact that 70% of new drugs or indications - in France, at least - represented no change or a step backwards from currently available interventions is not very encouraging. Where's the innovation? Sales techniques, it seems.

Drug Reps: The Telemarketer Script

A large amount of pharmaceutical company promotional dollars goes towards convincing physicians to prescribe their drugs. It's not all in the freebies either. Drug sales reps are often taught to follow a paricular script or adopt certain tactics depending on who they're dealing with. This 2007 PLoS Medicine paper has some of the details based on a former rep's experience and expert testimony.(Click to enlarge)

The full text is freely available at the above link.

GSK acquires Sirtris Pharmaceuticals

Pharm giant GlaxoSmithKline acquired Sirtris Pharmaceuticals for the tidy sum of $720 million US last week.

This story is interesting not because of the excitement of corporate deals and stock market fluctuations, but because Sirtris Pharmaceuticals specializes in developing small molecule activators of SirT1. And anything involving SirT1 - my protein of interest - is inherently fascinating.

It's actually more interesting for other reasons. Previously on this blog, I've echoed a sentiment common in the skeptical blogosphere: There's no such thing as alternative medicine. Once a treatment has been shown to work, it becomes part of mainstream medicine. Resveratrol, a polyphenol, is a SirT1 activator. SirT1 (I told you it was interesting) has been shown to be involved in insulin signaling, energy metabolism and lifespan extension in model organisms. Other work has shown resveratrol to have cardioprotective and anti-cancer effects. Resveratrol has long been thought to be a molecule behind the 'drink red wine' wisdom.

This all sounds great. And 'alties' probably feel vindicated: Resveratrol has been on sale in health food and dietary supplement stores for ages. Before many of the studies mentioned above had been done, in fact. But don't go reaching for your wineskin just yet. Studies have also shown that oral resveratrol has poor bioavailability.

That's where Sirtris comes in. They develop compounds that are analogs of resveratrol to improve potency and bioavailability (and patentability), and test those compounds. And Big Pharma (GSK) has taken notice, decided this is viable science, and acquired Sirtris in the hopes of turning these compounds into diabetes, anti-obesity or anti-aging drugs. Like other examples we've discussed this is a case of a natural or alternative medicine becoming mainstream (or, rather, the beginning steps of that process).

The moral of the story isn't that natural products work. In this case it doesn't - all resveratrol supplements will give you is expensive urine. The point is that if the science is there, the medicine will come.

There's still a possibility that these compounds will fail for one reason or another. Perhaps they won't be effective in humans as in rodents. Maybe there will be toxicity issues. If this happens, no doubt that Big Pharma conspiracy theorists will jump up and down saying that GSK made the purchase to squash a promising natural medicine. An almost 1 billion dollar investment seems to be a bit much for such a petty goal. If I was the big, evil corporation, I'd sink that money into the supplement makers and keep it on the shelves. But shrewd companies know that a tested drug has more value than an untested one. The only reason not to get science onside is if you don't think it will support you.

Corporate Profits Take Priority over Breast Cancer Prevention?

A recent Nature article describes the cancellation of a planned NIH trial (STELLAR) that would have compared the effects of newcomer drug Letrozole to the older Raloxifene in preventing breast cancer in post-menopausal women. While many potentially valid reasons were offered for the cancellation, other issues raised give cause to question whether the North American approach to cancer drug development is fatally flawed:

"the panel was strongly influenced by the fact that letrozole, made by Novartis, goes off-patent in 2011."

Translation: Who cares if letrozole prevents breast cancer if a corporate monopoly won't have the chance to exploit for ridiculous profits?

Hopefully this statement was issued by a disgruntled colleague and the Novartis bottom line doesn't really determine NIH trial funding decisions. Did Novartis threaten to drop their $30M/free drug contribution to the US government's $55M investment? Why should Novartis' interests be the only priority here? Once the drug is off-patent, it would available for generic production and even more accessible to patients. Must we always look for financial "returns" to justify investment in medical research? Isn't improving human health enough of a payback? Maybe it's about time North American governments reclaim some capital from the private sector to support publicly-funded research that benefits human beings instead of accountants.

Will Bill Gates Fix Science?

• "Four reasons why academic research is broken", a great little article by Jason over at Unsought Input. He raises some great points regarding the current sad state of access to scientific information and how its hurts society. I think the article's right on the money. I especially like the thing about citations - the way journals cite literature is just like so 1940s.

• On a more optimistic note, the Gates Foundation, now backed by the fortunes of the world's richest two men (Bill Gates and Warren Buffet) is changing the landscape of drug development with its mission of prioritizing humanitarian project funding. Even the big pharmas are starting to shake in their boots and will probably have to fall into line and also start developing AIDS drugs and vaccines for underprivileged majority who need them. Serves them right for being so damn greedy in the first place. One cool project that the Gates Foundation is helping to make happen is Jay Keasling's engineering of bacteria to synthesize cheap anti-malarials. Throwing $43 million at project such as this one, which will eventually make a curative dose of Artemisinin available for a quarter, you can see why big pharmas are sleeping with one eye open.

• Finally, just to prove that the bayblab is way ahead of mainstream science: a new study describing a method to distinguish organic from non-organic produce based on measurements of nitrogen isotope content.