I haven't mentioned Merck's mighty acquisition of Sirna yet - 1.1 billion dollars, eh? If anyone didn't think that RNA interference was hot, that kind of money should change their mind.

But still. . .antisense DNA was hot at one time, too, and then it cooled off considerably. It's come back in recent years, admittedly, as painful progress has been made. In fact, one of the big deals that showed that antisense was taken seriously again was made by. . .Merck, come to think of it. They had a big collaboration with ISIS for diabetes and (I believe) some other indications, but it didn't work out well. That press release has ISIS putting a brave face on having their clinical candidate thrown back over the fence, with talk of taking it on into clinical trials themselves. Four years later, it's still listed as Phase II on the company's website, which isn't a good sign, I think.

The rest of that 2002 press release is also instructive. The Phase III PKC-alpha compound they mention working on with Lilly bit the dust the next year, for one thing. And the ICAM-1 inhibitor met a similar fate in 2004. The 2002 story mentions the company having six products in Phase II, and now, according to their chart, they have five. None of those six candidate have progressed, and no doubt there's been some turnover along the way.

I'm not trying to be hard on ISIS. It's just that antisense DNA therapies have been extraordinarily hard to develop, and I see no reason why RNA interference will not have exactly the same sorts of problems. Small nucleic-acid based compounds are going to be hard, no matter what. It's interesting to note that Merck didn't just up and buy ISIS back then. But they're more desperate to fill their pipeline than they were back in the late 1990s, so out comes the checkbook. Good luck to all concerned.