Glaxo Does a Deuterium Deal

Well, there's someone who certainly believes in the deuterated-drug idea! GlaxoSmithKline (GSK) has announced today that they've signed a deal with Concert Pharmaceuticals to develop these. There's a $35 million payment upfront, which I'm sure will be welcome in this climate, and various milestone and royalty arrangements from there on out. I know that the press story says that it's a "potential billion dollar deal", but you have to make a useless number of assumptions to arrive at that figure. Let's just say that the amount will be somewhere between that billion-dollar figure and... well, the $35 million that Glaxo's just put up.

Where things will eventually land inside that rather wide range is impossible to say. No one's taken such a compound all the way through development, and every one of them is going to be different. (Deuterium might be a good idea, but it ain't magic.) It looks like the first compound up for evaluation will be an HIV protease inhibitor, CTP-518, which is a deuterated version of someone's existing compound - Concert has filed paten applications on deuterated versions of both darunavir (WO2009055006) and atazanavir (WO2008156632). The hope is that CTP-518 will have an improved enough metabolic profile to eliminate the need to add ritonavir into the drug cocktail.

The company is also providing deuterated versions of three of GSK's own pipeline compounds for evaluation, which is interesting, since that's the sort of thing that Glaxo could do itself. In fact, that's one of the key points to the whole deuterated-compound idea: the window of opportunity. Deuteration isn't difficult chemistry, and the applications for it in improving PK and tox profiles are pretty obvious (see below). It's a good bet that drug company patent applications will hencrforth include claims (and exemplified compounds) to make sure that deuterated versions of drug candidates can't be poached away by someone else. This strategy has a limited shelf life, but it's long enough to be potentially very profitable indeed.

One more note about that word "obvious". Now that people are raising all kinds of money and interest with the idea, sure, it looks obvious. And I'm sure that it's a thought that many people have had before - and then said "Nah, that's too funny-sounding. Might not work. And besides, you might not be able to patent it.

And besides, if it were that good an idea

, someone else would have already done it. There must be a good reason why no one's done it, you know". Getting up the nerve to try these things, that's the hard part. Roger Tung and Concert (and the other players in this field) deserve congratulations for not being afraid of the obvious.

Comments

[traden4alpha:]

This does look like an interesting approach to further optimizing the PK of medicines. Clever substitution of heavy hydrogen for regular hydrogen will change reaction rates to improve the amount of drug that does what it's supposed to (with less risks than more aggressive approaches such a halogenation). I'm sure they are also creating tritium-based variants for cancer drugs -- the tritiated molecule binds with something in the tumor and releases the very weak beta radiation of tritium at the cancer site.

But this seems like no panacea in the patent department. If a drug company includes deuterated variants in their initial patent application, then the deuterated version will go off-patent at the same time as the non-deuterated version. And if they don't patent the deuterated version at the same time, then others might do it. It's also unclear how the FDA will handle this. Does each new deuterated variant require a new full-scale phased clinical trial?

The real key to making this work is advanced in silico techniques that let new drug developers quickly decide which hydrogen atoms to replace with deuterium for the highest performance. That way, the best molecule will be patented and go straight to trials, approvals, and use.

Jun 02 12:48 PM

[Jasper M:]

I was trained as a physicist, and use to work in pharma, and I have a sneaking suspicion . . .

For some time now, pharma companies have been marketing incremental changes to drug cocktails. Started as a way to artificially extend patent protection (it's 'New' - New patent!), later as a way to continue premium sales in the face of competition from generic versions of original formulae.

I would not be the Least bit surprised to find that selling deuterated versions of pre-existing formulae was just a 21st century version of this.

And the fact that I am even considering this is a sign of how much trust in the medical profession has ebbed.

Jun 02 03:26 PM