Heavy Atoms and Hard Times

There's a deal that was announced this morning in the pharmaceutical business that shows two (nearly contradictory) things at the same time. Concert Pharmaceuticals, a start-up company in Massachusetts, has partnered with behemoth GlaxoSmithKline to develop a series of compounds which might show improved blood levels and toxicity profiles compared to existing drugs. So far, so good - deals like this happen all the time. But there's an odd feature here.


Concert's whole business plan revolves around deuterium, a heavy isotope of hydrogen. Drug molecules, like all compounds in organic chemistry, tend to bristle with hydrogen atoms, and these are often the first things attacked by liver enzymes once a drug is dosed. Metabolism of this type can clear the drug out of the bloodstream more quickly than one would like, produce a new metabolite compound with side effects of its own, or interfere with the usual clearance of other drugs being taken at the same time. It's a big issue in the development of any new compound.

But if you substitute a deuterium for one of those hydrogens that gets chewed off, things change. Now that chemical bond to the hydrogen atom is harder to break, because it's attached to something weightier. (Thinking of two weights attached to ends of a spring is, for once, a pretty good model of what's going on). If you pick your D-for-H swaps carefully, you can batten down an existing drug molecule so it lasts longer in the bloodstream, makes fewer side products, and so on. Improved molecule, benefit to patients, new chemical entity, fresh patent rights: you've just absorbed Concert's business plan.

This is all fine - in fact, as I point out on my blog this morning, the company and its founders deserve a lot of credit for giving this idea a fair hearing. It may sound like an obvious winner the way I've presented it, but I'm just (ahem) unnaturally convincing. I can tell you that this is the sort of idea that has surely occurred to many other pharma researchers over the years, who've thought about it a bit and said "Nah. . .someone else must have tried that already".

One downside is that it's an idea with an expiration date. If this works (and it's already working to the tune of many tens of millions of dollars, at any rate), you can be sure that every other drug company will batten down its patent filings from here on out to make sure that they own the deuterium versions of their new drug candidates. For now, Concert (and their competitors in the deuteration business) have been filing patents on every existing drug they can think of where the technique might show a benefit. My guess, though, is that everything that's usable has been claimed by now.

So that's one side of the story - ingenuity and innovation. But the other side is that, well, this ingenious idea is mostly going to furnish new (and presumably better) versions of things that we already know about. It's no secret that drug discovery has gotten harder and harder over the years (well, it's no secret to those of us who do it, I can tell you!) And as the screws slowly tighten, all kinds of ideas start to sound reasonable. Perhaps this one was just waiting for the times to get tough enough.

Presented by

Derek Lowe

Derek Lowe is a drug discovery chemist with 20 years of experience in the pharmaceutical industry, which is still very much his day job. He's worked on projects targeted at Alzheimer's, cancer, diabetes, infectious diseases, and other areas, but like most discovery scientists in the business, he has yet to produce a marketed drug. Explaining how and why this happens is what led to the launch of his blog, "In the Pipeline", in 2002, and the explaining continues. . .

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